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EP2427591A1 - Dispositif d'inhalation médical - Google Patents

Dispositif d'inhalation médical

Info

Publication number
EP2427591A1
EP2427591A1 EP20100719859 EP10719859A EP2427591A1 EP 2427591 A1 EP2427591 A1 EP 2427591A1 EP 20100719859 EP20100719859 EP 20100719859 EP 10719859 A EP10719859 A EP 10719859A EP 2427591 A1 EP2427591 A1 EP 2427591A1
Authority
EP
European Patent Office
Prior art keywords
group
coating
component
oxygen
diamond
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP20100719859
Other languages
German (de)
English (en)
Inventor
Moses M. David
Daniel R. Hanson
Philip A. Jinks
Christopher G. Blatchford
Vicki M. Lietzau
Jean A. Kelly
Suresh Iyer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
3M Innovative Properties Co
Original Assignee
3M Innovative Properties Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 3M Innovative Properties Co filed Critical 3M Innovative Properties Co
Publication of EP2427591A1 publication Critical patent/EP2427591A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C16/00—Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes
    • C23C16/22—Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes characterised by the deposition of inorganic material, other than metallic material
    • C23C16/30—Deposition of compounds, mixtures or solid solutions, e.g. borides, carbides, nitrides
    • C23C16/32—Carbides
    • C23C16/325—Silicon carbide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/009—Inhalators using medicine packages with incorporated spraying means, e.g. aerosol cans
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/26—Web or sheet containing structurally defined element or component, the element or component having a specified physical dimension
    • Y10T428/263—Coating layer not in excess of 5 mils thick or equivalent
    • Y10T428/264—Up to 3 mils
    • Y10T428/265—1 mil or less
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/31504—Composite [nonstructural laminate]
    • Y10T428/31652—Of asbestos
    • Y10T428/31663—As siloxane, silicone or silane
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/31504—Composite [nonstructural laminate]
    • Y10T428/31652—Of asbestos
    • Y10T428/31667—Next to addition polymer from unsaturated monomers, or aldehyde or ketone condensation product

Definitions

  • the present invention relates to medicinal inhalation devices and components for such devices as well as methods of making such devices and components.
  • Medicinal inhalation devices including pressurized inhalers, such as metered dose pressurized inhalers (MDIs), and dry powder inhalers (DPIs), are widely used for delivering medicaments.
  • pressurized inhalers such as metered dose pressurized inhalers (MDIs), and dry powder inhalers (DPIs)
  • MDIs metered dose pressurized inhalers
  • DPIs dry powder inhalers
  • Medicinal inhalation devices typically comprise a plurality of hardware components, (which in the case of a MDI can include for example gasket seals; metered dose valves (including their individual components, such as ferrules, valve bodies, valve stems, tanks, springs retaining cups and seals); containers; and actuators) as well as a number of internal surfaces which may be in contact with the medicinal formulation during storage or come in contact with the medicinal formulation during delivery.
  • a desirable material for a particular component is found to be unsuitable in regard to its surface properties, e.g., surface energy, and/or its interaction with the medicinal formulation.
  • the relatively high surface energy of materials typically used in MDIs can cause medicament particles in suspension formulations to adhere irreversibly to the surfaces of corresponding component(s), which has a consequent impact on the uniformity of medicinal delivery. Similar effects are also observed for DPIs.
  • Other examples of potentially undesirable interactions between a component and the medicinal formulation may include enhanced medicament degradation; adsorption of medicament or permeation of a formulation constituent or extraction of chemicals from plastic materials. For DPIs often permeation and adsorption of ambient water pose issues.
  • a method of making a medicinal inhalation device or a component of a medicinal inhalation device comprising a step of forming by plasma deposition under ion bombardment conditions a non-metal coating on at least a portion of a surface of the medicinal inhalation device or a component of a medicinal inhalation device, respectively, wherein the formed non-metal coating is a diamond-like glass comprising hydrogen and on a hydrogen free basis about 20 to about 40 atomic percent of silicon, greater than 39 atomic percent of carbon, and less than 33 down to and including zero atomic percent of oxygen.
  • Additional aspects of the present invention include: devices and components made in accordance with aforesaid method.
  • a medicinal inhalation device or a component of a medicinal inhalation device comprising a diamond-like glass coating on at least a portion of a surface of the device or component, respectively, said diamond- like glass comprising hydrogen and on a hydrogen free basis about 20 to about 40 atomic percent of silicon, greater than 39 atomic percent of carbon, and less than 33 down to and including zero atomic percent of oxygen.
  • Aforesaid diamond-like glasses may be described as oxygen-lean to oxygen free diamond-like glasses where in every case the content of carbon is greater than the content of oxygen.
  • diamond-like glass coatings advantageously allows for the provision of a system on the surface(s) of said devices and components having desirable structural integrity and/or surface characteristics.
  • diamond-like glass coatings show desirable expansion-capabilities together with marked flexibility, such properties being generally, continually further enhanced as the oxygen content approaches zero.
  • These properties have been found to be particularly advantageous e.g., in regard to aerosol containers and the manufacture of pressurized metered dose inhalers where conventional metered dose valves are crimped onto aerosol containers.
  • diamond- like glass coatings provided on an interior surface of such containers advantageously resist cracking upon crimping operations.
  • such diamond-like glass coatings may show desirable surface characteristics, in particular barrier and/or passivation characteristics. Further, such diamond-like glass coatings may also have advantageously low surface energies.
  • Medicinal inhalation devices and components in particular medicinal inhalation devices comprising such components
  • diamond-like glass coatings described herein are particularly advantageous for use as coatings in medicinal inhalation devices or components thereof either alone or alternatively as a coating onto which a composition comprising an at least partially fluorinated compound is applied or alternatively treating at least a portion of a surface of the diamond- like glass coating with fluorine-containing gas plasma.
  • Dependent claims define further embodiments of the invention.
  • the invention in its various combinations, either in method or apparatus form, may also be characterized by the following listing of items:
  • a method of making a medicinal inhalation device or a component of a medicinal inhalation device comprising a step of forming by plasma deposition under ion bombardment conditions a non-metal coating on at least a portion of a surface of the device or the component, respectively, wherein the non-metal coating formed is a diamond-like glass comprising hydrogen and on a hydrogen free basis from about 20 to about 40 atomic percent of silicon, greater than 39 atomic percent of carbon, and less than 33 down to and including zero atomic percent of oxygen.
  • the diamond- like glass contains on a hydrogen free basis from about 20 to about 40 atomic percent of silicon, greater than 42 atomic percent of carbon, less than 30 down to and including zero atomic percent of oxygen
  • the diamond- like glass contains on a hydrogen free basis from about 20 to about 40 atomic percent of silicon, greater than 50 atomic percent of carbon, less than 25 down to and including zero atomic percent of oxygen
  • non-metal coating is substantially free of fluorine, in particular free of fluorine.
  • non-metal coating is substantially free of nitrogen, in particular free of nitrogen; and/or wherein the non-metal coating is substantially free of sulfur, in particular free of sulfur.
  • a method according to any one of the preceding claims, wherein the forming the non-metal coating comprises ionizing a gas comprising an organosilicon.
  • the organosilicon is selected from the group consisting of trimethylsilane, triethylsilane, trimethoxysilane, triethoxysilane, tetramethylsilane, tetraethylsilane, tetramethoxysilane, tetraethoxysilane, hexamethylcyclotrisiloxane, tetramethylcyclotetrasiloxane, tetraethylcyclotetrasiloxane, octamethylcyclotetrasiloxane, hexamethyldisiloxane, bistrimethylsilylmethane, and mixtures thereof, in particular the organosilicon is selected from the group consisting of trimethylsilane, triethylsilane, tetramethylsilane, tetraethylsilane, hexamethyl- cyclotrisiloxane, bistri
  • said gas further comprises oxygen gas, where the amount of oxygen gas is less than 35% on a molar basis in the said gas, in particular less than 30 % on a molar basis in said gas; and/or wherein during ionizing of said gas comprising said organosilicon, said gas further comprises an oxygen gas and/or said gas comprises an organosilicon comprising oxygen and wherein the atomic ratio of oxygen (O) to silicon (Si) in said gas is equal to or less than 3 : 1, in particular equal to or less than 2.5 : 1, more particularly equal to or less than 1 : 1, most particularly equal to or less than 0.8 : 1.
  • the non-metal coating formed on said surface has a thickness greater than 100 nm, in particular a thickness equal to or greater than 250 nm, more particularly a thickness greater than 550 nm; and/or the non-metal coating formed on said surface has a thickness equal to or less than 5000 nm, in particular a thickness equal to or less than 3500 nm, more particularly a thickness equal to or less than 2500 nm, most particularly a thickness equal to or less than 2000 nm.
  • the fluorine-containing-gas-plasma comprises a fluorine-containing compound selected from the group consisting of fluorine (F2); nitrogentrifluoride (NF 3 ); sulfurhexafluoride (SF 6 ); silicontetrafluorine (SiF 4 ); phosphorustrifluoride (PF 3 ); carbon tetrafluoride (CF 4 ); perfluoroethane (C 2 F 6 ); perfluoropropane (C 3 F 8 ), perfluorobutane (C 4 Fi 0 ) and perfluoropentane (C 5 F 12 ) and their isomeric forms; hexafluoropropylene (HFP) trimer; 2,2,3-trifluoro-3- (trifluoromethyl)oxirane (C 3 F 6 O) and mixtures thereof.
  • fluorine fluorine
  • NF 3 nitrogentrifluoride
  • SiF 4 sulfurhexafluoride
  • PF 3 silicontetrafluorine
  • said at least partially fluorinated compound comprises at least one functional group and said non-metal coating has at least one functional group, wherein the non-metal coating is provided with said at least one functional group during the forming step or after the forming step the formed non-metal coating is treated to provide the non-metal coating with said at least one functional group, and wherein the method further comprises a step of: allowing at least one functional group of the at least partially fluorinated compound to react with at least one functional group of the non-metal coating to form a covalent bond.
  • said at least one functional group of the non-metal coating having an active hydrogen is selected from the group consisting of a hydroxyl group (-OH) and a carboxyl group (-COOH), in particular a hydroxyl group (-OH).
  • said at least one functional group of the at least partially fluorinated compound is a silane group, in particular a silane group comprising at least one hydrolyzable group, more particularly at least two hydrolyzable groups, and most particularly three hydrolyzable groups.
  • said at least partially fluorinated compound comprises a polyfluoropolyether segment, in particular a perfluorinated polyfluoropolyether segment.
  • said at least partially fluorinated compound comprises a perfluorinated polyfluoropolyether segment, wherein the repeating units of the perfluorinated polyfluoropolyether segment the number of carbon atoms in sequence is at most 6, in particular at most 4, more particularly at most 3 and most particularly at most 2.
  • the at least partially fluorinated compound is a polyfluoropolyether silane, in particular a multifunctional polyfluoropolyether silane, and more particularly a difunctional polyfluoropolyether silane.
  • composition comprises a monofunctional polyfluoropolyether silane and a multifunctional polyfluoropolyether silane, in particular a difunctional polyfluoropolyether silane; and/or wherein the polyfluoropolyether segment(s) of the polyfluoropolyether silane is (are) not linked to the functional silane group(s) via a functionality that includes a nitrogen-silicon bond or a sulfur-silicon bond.
  • polyfluoropolyether segment(s) of the polyfluoropolyether silane is (are) linked to the functional silane group(s) via a functionality that includes a carbon-silicon bond.
  • polyfluoropolyether segment(s) of the polyfluoropolyether silane is (are) linked to the functional silane group(s) via a -C(R) 2 -Si functionality where R is independently hydrogen or a Ci_ 4 alkyl group, more particularly hydrogen.
  • R/ is a monovalent or multivalent polyfluoropolyether segment
  • Q is an organic divalent or trivalent linking group
  • each R is independently hydrogen or a Ci_ 4 alkyl group
  • each Y is independently a hydrolyzable group
  • R la is a Ci_8 alkyl or phenyl group; x is 0 or 1 or 2; y is 1 or 2; and z is 1, 2, 3, or 4.
  • the polyfluoropolyether segment, R/ comprises perfluorinated repeating units selected from the group consisting Of -(C n F 2n O)-, -(CF(Z)O)-, -(CF(Z)C n F 2n O)-, -(C n F 2n CF(Z)O)-, -(CF 2 CF(Z)O)-, and combinations thereof; wherein n is an integer from 1 to 6 and Z is a perfluoroalkyl group, an oxygen- containing perfluoroalkyl group, a perfluoroalkoxy group, or an oxygen-substituted perfluoroalkoxy group, each of which can be linear, branched, or cyclic, and have 1 to 5 carbon atoms and up to 4 oxygen atoms when oxygen-containing or oxygen-substituted and wherein for repeating units including Z the number of carbon atoms in sequence is at most 6.
  • n is an integer from 1 to 4 and wherein for repeating units including Z the number of carbon atoms in sequence is at most four, in particular wherein n is an integer from 1 to 3 and wherein for repeating units including Z the number of carbon atoms in sequence is at most three.
  • polyfluoropolyether segment, R/ comprises perfluorinated repeating units selected from the group consisting Of -(C n F 2n O)-, -(CF(Z)O)-, and combinations thereof; wherein n is 1 or 2 and Z is an -CF3 group.
  • each hydrolyzable group is independently selected from the group consisting of hydrogen, halogen, alkoxy, acyloxy, polyalkyleneoxy, and aryloxy groups, in particular wherein each hydrolyzable group is independently selected from the group consisting of alkoxy, acyloxy, aryloxy, and polyalkyleneoxy groups, more particularly wherein each hydrolyzable group is independently an alkoxy group, in particular an alkoxy group -OR' wherein each R' is independently a C 1-6 alkyl, more particularly a C 1-4 alkyl.
  • weight average molecular weight of the polyfluoropoly ether segment is about 900 or higher, in particular about 1000 or higher; and/or the weight average molecular weight of the polyfluoropolyether segment is about 6000 or less, in particular about 4000 or less, more particularly about 3000 or less.
  • composition comprises at least the following two polyfluoropolyether silanes in accordance with Formula Ia: (a) a first polyfluoropolyether silane wherein R/ is C 3 F 7 O(CF(CF 3 )CF 2 O) P CF(CF 3 )-, and Q-C(R) 2 -Si(Y')3-x(R la )x is C(O)NH(CH 2 ) 3 Si(OR') 3 , wherein p is 3 to 50, in particular wherein p is from about 3 to about 20, more particularly p is from about 4 to about 10; and
  • R' is methyl or ethyl; and/or wherein either the composition comprises a catalyst and the composition comprises at least a total of 0.1 wt % of said first and second polyfluoropolyether silanes, or the composition is free of catalyst and the composition comprises at least a total of one (1) wt % of said first and second polyfluoropolyether silanes.
  • a method according to claim 51 or claim 52, wherein the weight percent ratio of the first to second polyfluoropolyether silane (first polyfluoropolyether silane : second polyfluoropolyether silane) in the composition is equal to or greater than 10 : 90, in particular equal to or greater than 20 : 80, more particularly equal to or greater than 30 : 70, most particularly equal to or greater than 40 : 60; and/or wherein the weight percent ratio of the first to second polyfluoropolyether silane (first polyfluoropolyether silane : second polyfluoropolyether silane) in the composition is equal to or less than 99 : 1 , in particular equal to or less than 97 : 3, most particularly equal to or less than 95 : 5.
  • the composition comprising an at least partially fluorinated compound further comprises an organic solvent, in particular an organic solvent that is a fluorinated solvent and/or a lower alcohol.
  • composition comprising an at least partially fluorinated compound further comprises an acid.
  • composition comprising an at least partially fluorinated compound further comprises water and/or a non- fluorinated cross-linking agent, in particular a cross-linking agent comprising one or more non-fluorinated compounds, each compound having at least two hydrolyzable groups per molecule.
  • composition comprises a non-fluorinated compound and the non-fluorinated compound is a compound in accordance to Formula II: where R 5 represents a non-hydrolyzable group; Y 2 represents a hydrolyzable group; and g is 0, 1 or 2.
  • cross-linking agent comprises a compound selected from the group the consisting of tetramethoxysilane, tetraethoxysilane, tetrapropoxysilane, tetrabutoxysilane, methyl triethoxysilane, dimethyldiethoxysilane, octadecyltriethoxysilane, 3-glycidoxypropyltriethoxysilane, 3- aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3- trimethoxysilylpropylmethacrylate, and mixtures thereof.
  • a medicinal inhalation device or a component of a medicinal inhalation device made according to any one of claims 1 to 63.
  • a medicinal inhalation device or a component of a medicinal inhalation device comprising a diamond-like glass coating on at least a portion of a surface of the device or the component, respectively, said diamond-like glass comprising hydrogen and on a hydrogen free basis about 20 to about 40 atomic percent of silicon, greater than 39 atomic percent of carbon, and less than 33 down to and including zero atomic percent of oxygen.
  • the diamond-like glass contains on a hydrogen free basis from about 20 to about 40 atomic percent of silicon, greater than 42 atomic percent of carbon, less than 30 down to and including zero atomic percent of oxygen
  • a device or a component according to any one of claims 65 to 71 wherein, on a hydrogen- free basis, the content of silicon in the diamond-like glass is in the range from about 20 to about 35 atomic percent.
  • 73. A device or a component according to any one of claims 65 to 72, said coating being plasma deposited under ion bombardment conditions; and/or wherein the diamond-like glass coating is covalently bonded to the at least a portion of a surface of the device or the component, respectively.
  • a device or a component according claim 77 said diamond-like glass coating being post-treated with a fluorine-containing gas plasma, said fluorine-containing-gas-plasma comprising a fluorine-containing compound selected from the group consisting of fluorine (F2); nitrogentrifluoride (NF 3 ); sulfurhexafluoride (SF 6 ); silicontetrafluorine (SiF 4 ); phosphorustrifluoride (PF3); carbon tetrafluoride (CF 4 ); perfluoroethane (C 2 F 6 ); perfluoropropane (C3F8), perfluorobutane (C 4 F 1 O) and perfluoropentane (CsF 12 ) and their isomeric forms; hexafluoropropylene (HFP) trimer; 2,2,3-trifluoro-3- (trifluoromethyl)oxirane (CsF 6 O) and mixtures thereof.
  • fluorine fluorine
  • NF 3 nitrogentriflu
  • a device or a component according to claim 79, wherein the at least partially fluorinated compound comprises at least one functional group which shares at least one covalent bond with the diamond-like glass coating.
  • a device or a component according to claim 80 wherein the fluorine-containing coating is covalently bonded to the diamond-like glass coating through a plurality of covalent bonds.
  • a device or a component according to claim 81 wherein the fluorine-containing coating is covalently bonded to the diamond-like glass coating through a plurality of covalent bonds including bonds in O-Si groups, in particular bonds in Si-O-Si groups.
  • the at least partially fluorinated compound comprises a perfluorinated polyfluoropolyether segment, where in the repeating units of the perfluorinated polyfluoropolyether segment the number of carbon atoms in sequence is at most 6, in particular at most 4, more particularly at most 3 and most particularly at most 2.
  • a device or a component according to claim 86 wherein the polyfluoropolyether segment(s) is (are) not linked to the silane group(s) via a functionality that includes a nitrogen-silicon bond or a sulfur-silicon bond.
  • fluorine-containing coating is a polyfluoropolyether-containing coating comprising polyfluoropolyether silane entities of the following Formula Ib:
  • R/ is a monovalent or multivalent polyfluoropolyether segment
  • Q is an organic divalent or trivalent linking group; each R is independently hydrogen or a C 1-4 alkyl group;
  • R la is a Ci_8 alkyl or phenyl group; x is 0 or 1 or 2; y is 1 or 2; and z is 1, 2, 3, or 4. 90.
  • n is an integer from 1 to 4 and wherein for repeating units including Z the number of carbon atoms in sequence is at most four.
  • n is an integer from 1 to 3 and wherein for repeating units including Z the number of carbon atoms in sequence is at most three, more particularly the polyfluoropolyether segment, R/, comprises perfluorinated repeating units selected from the group consisting of -(C n F 2n O)-, - (CF(Z)O)-, and combinations thereof; wherein n is 1 or 2 and Z is an -CF3 group.
  • R f is selected from the group consisting of C 3 F 7 O(CF(CF 3 )CF 2 O) P CF(CF 3 )-, CF 3 O(C 2 F 4 O) P CF 2 -, C 3 F 7 O(CF(CF 3 )CF 2 O) p CF 2 CF 2 -,C 3 F 7 O(CF 2 CF 2 CF 2 O) p CF 2 CF 2 -, C 3 F 7 O(CF 2 CF 2 CF 2 O) P CF(CF 3 )- and CF 3 O(CF 2 CF(CF 3 )O) P (CF 2 O)X-, wherein X is CF 2 -, C 2 F 4 -, C 3 F 6 -, or C 4 F8- and wherein the average value of p is 3 to 50.
  • weight average molecular weight of the polyfluoropoly ether segment is about 900 or higher, in particular 1000 or higher; and/or the weight average molecular weight of the polyfluoropolyether segment is about 6000 or less, in particular about 4000 or less, more particularly about 3000 or less.
  • fluorine-containing coating comprises at least the following two polyfluoropolyether silane entities in accordance with Formula Ib:
  • R/ is -CF 2 O(CF 2 O) m (C 2 F 4 O) p CF 2 -, and Q-C(R) 2 -Si(O-) 3 .
  • x (R la ) x is C(O)NH(CH 2 ) 3 Si(O-) 3 and wherein m is 1 to 50 and p is 3 to 40, in particular wherein the average value of m+p or p is from about 4 to about 24, more particularly wherein m and p are each about 9 to aboutl2
  • a device or a component according to claim 104 wherein the weight percent ratio of the first to second polyfluoropolyether silane entity (first polyfluoropolyether silane entity
  • second fluoropolyether silane entity is equal to or greater than 10 : 90, in particular equal to or greater than 20 : 80, more particularly equal to or greater than 30 : 70, most particularly equal to or greater than 40 : 60; and/or wherein the weight percent ratio of the first to second polyfluoropolyether silane (first polyfluoropolyether silane : second polyfluoropolyether silane) is equal to or less than 99 : 1, in particular equal to or less than 97 : 3, most particularly equal to or less than 95 : 5.
  • fluorine-containing coating has a thickness greater tan 15 Angstroms, in particular at least about 2 nm, more particularly at least about 10 nm, even more particularly at least about 25 nm, and most preferably at least about 40 nm; and/or wherein the fluorine-containing coating has a thickness of at most about 200 nm, in particular at most about 150 nm, more particularly at most about 100 nm.
  • a device according to claim 114 wherein said surface of the metered dose inhaler is at least the interior surface of the aerosol container, in particular an aerosol container made of aluminum, aluminum alloy, stainless steel, glass, or a polymer.
  • said surface of the metered dose inhaler is all interior surfaces that is or will come in contact with the medicinal aerosol formulation during storage or delivery from the metered dose inhaler.
  • the medicinal aerosol formulation comprises a medicament that is dispersed in said formulation; and/or the medicinal aerosol formulation comprises a chloride and/or a bromide salt of a medicament; and/or the medicinal aerosol formulation comprises a corticosteroid, in particular a 20-ketosteroid, more particular a 20-ketosteroid including an -OH group at the Cl 7 and/or C21 position.
  • the medicinal aerosol formulation comprises a medicament that is dispersed in said formulation and wherein the medicinal aerosol formulation comprises at most 0.005 wt % with respect to the formulation of surfactant and/or less than 5 wt % with respect to the formulation of ethanol.
  • a device according to any one of claims 114 to 118, wherein the medicinal aerosol formulation is substantially free of surfactant, in particular free of surfactant, and/or wherein the medicinal aerosol formulation is substantially free, in particular free of ethanol.
  • the medicinal aerosol formulation comprises a medicament selected from the group consisting of salbutamol, terbutaline, ipratropium, oxitropium, tiotropium, daratropium, aclidinium, beclomethasone, flunisolide, budesonide, mometasone, ciclesonide, cromolyn sodium, nedocromil sodium, ketotifen, azelastine, ergotamine, cyclosporine, salmeterol, fluticasone, formoterol, procaterol, indacaterol, TA2005, omalizumab, oglemilast, zileuton, insulin, pentamidine, calcitonin, leuprolide, alpha- 1 -antitrypsin, interferon, triamcinolone, and pharmaceutically acceptable salts and esters thereof and mixtures thereof.
  • a medicament selected from the group consisting of salbutamol, terbutaline, ipratrop
  • Figure Ia represents a schematic cross-sectional view of a pressurized metered dose inhaler known in the art and Figure Ib represents an enlarged view of a portion of the inhaler.
  • Figure 1 shows a metered dose dispenser (100), in particular an inhaler, including an aerosol container (1) fitted with a metered dose valve (10) (shown in its resting position).
  • a metered dose dispenser 100
  • an inhaler including an aerosol container (1) fitted with a metered dose valve (10) (shown in its resting position).
  • Aerosol containers for metered dose inhalers are typically made of aluminum or an aluminum alloy. Aerosol containers may be made of other materials, such as stainless steel, glass, plastic (e.g., polyethylene terephthalate, polycarbonate, polyethylene, high density polyethylene and polypropylene) and ceramics.
  • plastic e.g., polyethylene terephthalate, polycarbonate, polyethylene, high density polyethylene and polypropylene
  • valve is typically affixed, i.e., crimped, onto the container via a cap or ferrule (11) (typically made of aluminum or an aluminum alloy) which is generally provided as part of the valve assembly. Between the container and the ferrule there may be one or more seals. In the embodiments shown in Figures Ia and Ib between the container (1) and the ferrule (11) there are two seals including e.g., an O-ring seal (8) and the gasket seal (9).
  • the illustrated valve is a commercial valve marketed under the trade designation SPRAYMISER by 3M Company, St. Paul, Minnesota, USA.
  • the container/valve dispenser is typically provided with an actuator (5) including an appropriate patient port (6), such as a mouthpiece.
  • an appropriate patient port (6) such as a mouthpiece.
  • the patient port is generally provided in an appropriate form (e.g., smaller diameter tube, often sloping upwardly) for delivery through the nose.
  • Actuators are generally made of a plastic, for example polypropylene or polyethylene.
  • the inner walls (2) of the container and the outer walls of the portion(s) of the metered dose valve located within the container defined a formulation chamber (3) in which aerosol formulation (4) is contained.
  • aerosol formulation may be filled into the container either by cold-filling (in which chilled formulation (chilled to temperatures of about -50 to -55°C for propellant HFA 134a-based formulations) is filled into the container and subsequently the metered dose valve is crimped onto the container) or by pressure filling (in which the metered dose valve is crimped onto the container and then formulation is pressure filled through the valve into the container).
  • cold-filling in which chilled formulation (chilled to temperatures of about -50 to -55°C for propellant HFA 134a-based formulations) is filled into the container and subsequently the metered dose valve is crimped onto the container
  • pressure filling in which the metered dose valve is crimped onto the container and then formulation is pressure filled through the valve into the container.
  • the container/valve device After filling of the aerosol formulation and crimping on the valve, regardless of the order, typically the container/valve device is tested for leaks by immersing the device in a water bath for 3 minutes at 55°C.
  • An aerosol formulation used in a metered dose inhaler typically comprises a medicament or a combination of medicaments and liquefied propellant selected from the group consisting of HFA 134a, HFA 227 and mixtures thereof.
  • Aerosol formulations may, as desired or needed, comprise other excipients, such as surfactant, a co-solvent (e.g., ethanol), CO 2 , or a particulate bulking agent.
  • Medicament may be provided in particulate form (generally having a median size in the range of 1 to 10 microns) suspended (i.e., dispersed) in the liquefied propellant.
  • medicament may be in solution (i.e., dissolved) in the formulation.
  • a medicament may be a drug, vaccine, DNA fragment, hormone or other treatment.
  • the amount of medicament would be determined by the required dose per puff and available valve sizes, which are typically 25, 50 or 63 microlitres, but may include 100 microlitres where particularly large doses are required.
  • Suitable drugs include those for the treatment of respiratory disorders, e.g., bronchodilators, antiinflammatories (e.g., corticosteroids), anti-allergies, anti-asthmatics, anti-histamines, and anti-cholinergic agents.
  • Therapeutic proteins and peptides may also be employed for delivery by inhalation.
  • Exemplary drugs which may be employed for delivery by inhalation include but are not limited to: salbutamol, terbutaline, ipratropium, oxitropium, tiotropium, daratropium, aclidinium, beclomethasone, flunisolide, budesonide, mometasone, ciclesonide, cromolyn sodium, nedocromil sodium, ketotifen, azelastine, ergotamine, cyclosporine, salmeterol, fluticasone, formoterol, procaterol, indacaterol, TA2005, omalizumab, oglemilast, zileuton, insulin, pentamidine, calcitonin, leuprolide, alpha- 1 -antitrypsin, interferons, triamcinolone, and pharmaceutically acceptable salts and esters thereof such as salbutamol
  • Pressurized metered dose inhalers including e.g., metal aerosol containers whose interior surfaces are coated in accordance with certain aspects described herein are particularly advantageous for containing and delivering corticosteroids, particularly 20-ketosteroids, including those with an -OH group at the C17 and/or C21 position, such as budesonide, which may undergo degradation when in contact with metal oxides, as well as other medicaments, such as salbutamol, formoterol, salmeterol, TA2005 and salts thereof, which are susceptible to degradation when in contact with common container materials, such as aluminum.
  • corticosteroids particularly 20-ketosteroids, including those with an -OH group at the C17 and/or C21 position, such as budesonide, which may undergo degradation when in contact with metal oxides, as well as other medicaments, such as salbutamol, formoterol, salmeterol, TA2005 and salts thereof, which are susceptible to degradation when in contact with common container materials, such as aluminum.
  • Pressurized metered dose inhalers including e.g., metal aerosol containers (and metal valve components) whose interior surfaces are coated in accordance with certain aspects described herein are particularly advantageous for containing and delivering solution formulations containing chloride or bromide salts of medicaments, such as ipratropium bromide, oxitropium bromide, tiotropium bromide or pirbuterol hydrochloride, the presence of such electrolyte formulations in combination with for example uncoated aluminum containers and stainless steel valve components may cause an undesired formation of a galvanic cell.
  • chloride or bromide salts of medicaments such as ipratropium bromide, oxitropium bromide, tiotropium bromide or pirbuterol hydrochloride
  • Pressurized metered dose inhalers including e.g., aerosol containers (in particular metal aerosol containers) whose interior surfaces are coated in accordance with certain aspects described herein are particularly advantageous for containing and delivering medicinal aerosol formulations comprising a medicament that is dispersed in said formulation.
  • embodiments described in detail below are particularly useful in regard to pressurized metered dose inhalers including a medicinal aerosol formulation that includes low amounts of surfactant (at most 0.005 wt % with respect to the formulation); or is substantially free (less than 0.0001 wt % with respect to drug) or free of a surfactant.
  • embodiments described in detail below are particularly useful in metered dose inhalers including a medicinal aerosol formulation that contains low amounts of ethanol (less than 5 wt % with respect to the formulation), or is substantially free (less than 0.1 wt % with respect to the formulation) or free of ethanol.
  • the valve shown in Figure Ia better viewed in Figure Ib, includes a metering chamber (12), defined in part by an inner valve body (13), through which a valve stem (14) passes.
  • the valve stem which is biased outwardly by a compression spring (15), is in sliding sealing engagement with an inner tank seal (16) and an outer diaphragm seal (17).
  • the valve also includes a second valve body (20) in the form of a bottle emptier.
  • the inner valve body (referred to in the following as the "primary" valve body) defines in part the metering chamber.
  • the second valve body (referred to in the following as the "secondary" valve body) defines in part a pre-metering region or chamber besides serving as a bottle emptier.
  • aerosol formulation (4) can pass from the formulation chamber into a pre-metering chamber (22) provided between the secondary valve body (20) and the primary valve body (13) through an annular space (21) between the flange (23) of the secondary valve body and the primary valve body.
  • the valve stem (14) is pushed inwardly relative to the container from its resting position shown in Figures Ia and b, allowing formulation to pass from the metering chamber through a side hole (19) in the valve stem and through a stem outlet (24) to an actuator nozzle (7) then out to the patient.
  • valve stem (14) When the valve stem (14) is released, formulation enters into the valve, in particular into the pre-metering chamber (22), through the annular space (21) and thence from the pre-metering chamber through a groove (18) in the valve stem past the tank seal (16) into the metering chamber (12).
  • the components of such valves are made of metal (e.g., stainless steel, aluminum or aluminum alloy) or plastic.
  • metal e.g., stainless steel, aluminum or aluminum alloy
  • compression springs are generally made of a metal, in particular stainless steel as the conventional material.
  • Compression springs may also be made of aluminum or aluminum alloy.
  • Valve stems and valve bodies are generally made of metal and/or plastic; as a metal conventionally stainless steel is used (other metals that may be used include aluminum, aluminum alloy and titanium) and as plastics conventionally polybutylene terephthalate (PBT) and/or acetal are used (other polymers that may be used include polyetheretherketones, nylon, other polyesters (such as tetrabutylene terephthalate), polycarbonates and polyethylene).
  • a surface more favorably the entire surface, of a component or components of a medicinal inhalation device (e.g., aerosol containers, actuators, ferrules, valve bodies, valve stems or compression springs of metered dose inhalers or powder containers or carriers of dry powder inhalers) which is or will come in contact with a medicament or a medicinal formulation during storage or delivery from the medicinal inhalation device are treated according to methods described herein.
  • a component or components of a medicinal inhalation device e.g., aerosol containers, actuators, ferrules, valve bodies, valve stems or compression springs of metered dose inhalers or powder containers or carriers of dry powder inhalers
  • the entire surface of the component including any surface or surfaces (if present) that do not or will not come in contact with a medicament or a medicinal formulation during storage or delivery from the device, may also be treated according to methods described herein.
  • a compartment in a dry powder inhaler may be coated to reduce moisture permeation into it, in order to protect drug contained therein.
  • a component or components of a medicinal inhalation device favorably at least a portion of a surface, more favorably the entire surface, of a component or components of a medicinal inhalation device, which either come in contact with a movable component and/or are movable during storage or delivery from the medicinal inhalation device are treated according to methods described herein.
  • components for pressurized metered dose inhalers include e.g., aerosol containers, valve bodies, valve stems or compression springs of metered dose valves.
  • a component of a medicinal inhalation device in accordance with the present invention or made according to methods in accordance with the present invention is a component of a metered dose inhaler.
  • Said component may be selected from the group consisting of aerosol container, an actuator, a ferrule, a valve body (e.g., a primary and/or a secondary valve body), a valve stem and a compression spring.
  • a component of a medicinal inhalation device in accordance with the present invention or made according to methods in accordance with the present invention is a component of a dry powder inhaler.
  • Said component may be selected from the group consisting of a component that defines at least in part a powder container or carrier (e.g., a multidose reservoir container or single dose blister or capsule or tape), a component used to open a sealed powder container (e.g., piercer to open single dose blisters or capsules), a component that defines at least in part a deagglomeration chamber, a component of a deagglomeration system, a component that defines at least in part a flow channel, a dose- transporting component (e.g., a dosing rod, dosing wheel or dosing cylinder with a recess dimensioned to accommodate a single dose of powder trapped between said component and a housing in which it moves to transport the dose) , a component that defines at least in part a mixing chamber, a component that defines at least in part an actuation chamber (e.g., a holding chamber where a dose is dispensed prior to inhalation), a mouthpiece and a nosepiece.
  • Diamond-like-glass coatings as described herein may be favorably applied to a surface or surfaces along the flow path of drug in order to advantageously minimize residual drug adhering to such surfaces, in order to reduce drug loss resulting in inaccurate dosing, or to allow components to move relative to one another unimpeded by powder.
  • Embodiments in accordance with certain aspects of the present invention include forming by plasma deposition under ion bombardment conditions a non-metal coating on at least a portion of a surface of a medicinal inhalation device or a component of a medicinal inhalation device (e.g., an aerosol container of a metered dose inhaler, a metered dose valve or a component thereof, or a powder container or carrier of a dry powder inhaler), where the formed non-metal coating is a diamond-like glass comprising hydrogen and on a hydrogen free basis from about 20 to about 40 atomic percent of silicon, equal to or greater than 39 atomic percent of carbon, and less than 33 down to and including zero atomic percent of oxygen.
  • a non-metal coating is a diamond-like glass comprising hydrogen and on a hydrogen free basis from about 20 to about 40 atomic percent of silicon, equal to or greater than 39 atomic percent of carbon, and less than 33 down to and including zero atomic percent of oxygen.
  • Embodiments in accordance with other aspects of the present invention include a medicinal inhalation device or a component of a medicinal inhalation device comprising a diamond- like glass coating on at least a portion of a surface of the device or component, respectively, where the diamond-like glass coating comprising hydrogen and on a hydrogen free basis from about 20 to about 40 atomic percent of silicon, equal to or greater than 39 atomic percent of carbon, and less than 33 down to and including zero atomic percent of oxygen.
  • said coating is plasma deposited under ion bombardment conditions.
  • Such diamond-like glass coatings are advantageously covalently bonded to the at least a portion of the surface of the device or the component, respectively.
  • plasma deposition (which may be suitably microwave, inductively coupled, DC, AC or RF (radio frequency) plasma deposition, more suitably microwave, inductively coupled or RF plasma deposition, most suitably RF plasma deposition) is carried out in such a way that an ion sheath is formed upon generation of the plasma (plasma formed from an appropriate source compound or compounds, typically an organosilicon as discussed in more detail below) and where the substrate, whose surface is or surfaces are to be coated, is positioned within the plasma system so that during plasma deposition the substrate is within the ion sheath.
  • An explanation of the formation of ion sheaths can be found in Brian Chapman, Glow Discharge Processes, 153 (John Wily & Sons, New York 1980).
  • RF -plasma deposition this can be generally accomplished through the use of a RF- powered electrode and locating the substrate to be coated in proximity to the RF-powered electrode.
  • microwave plasma deposition and inductively coupled plasma deposition this can be accomplished by providing the microwave or inductively coupled plasma system, respectively, with an electrode, biasing (generally negatively biasing) this electrode and locating the substrate in proximity to said biased electrode.
  • biasing generally negatively biasing
  • DC plasma deposition this can be accomplished by locating the substrate in proximity to the cathode or negatively biased electrode (e.g., for providing thin coatings of 10 nm or less). In this manner plasma deposition occurs under conditions of ion bombardment.
  • polymerized species formed in the plasma are subjected to ion bombardment, and are thus among other things fragmented, before depositing and/or upon deposition on the substrate allowing the provision of an advantageous, dense, random, covalent system on the surface(s) of the substrate.
  • the substrate whose surface is or surfaces are to be coated, is located within an ion sheath, ions accelerating toward the electrode bombard the species being deposited from the plasma onto the substrate and thus the substrate is exposed to the ion bombarded species being deposited from the plasma.
  • the resulting reactive species within the plasma react on the surface of the substrate, forming a coating, the composition of which is controlled by the composition of the gas being ionized in the plasma.
  • the species forming the coating are advantageously attached to the surface of the substrate by covalent bonds, and therefore the coating is advantageously covalently bonded to the substrate.
  • amorphous covalent systems show excellent adhesion (through e.g., covalent bonding) to many substrate materials, including metals, polymers, glass and ceramics.
  • covalent amorphous systems provide "sharp" coatings e.g., on complex-formed components such as valve stems or compression springs.
  • Such covalent amorphous systems are desirable in that they are typically transparent or translucent.
  • Such amorphous covalent systems show advantageously high atomic packing densities, typically in a range from about 0.20 to about 0.28 (in particular from about 0.22 to about 0.26) gram atom number density in units of gram atoms per cubic centimeter.
  • Polymeric coatings e.g., plasma polymer coatings
  • Such high atomic packing densities allow the provision of coatings having a minimum of porosity, excellent resistance to diffusion to liquid or gaseous materials, and superb, "diamond-like" hardness.
  • Micro-hardness of diamond-like glass coatings described herein, as determined using a nanoindenter are generally, favorably at least 1 GPa, more favorably at least 2 GPa.
  • Such coatings may also have desirable surface characteristics, including e.g., poor wettability and low surface energy.
  • oxygen-lean to oxygen free diamond-like glass coatings described herein have been found to have superior structural integrity, first having desirable durability over the lifetime of medicinal inhalation device and secondly having desirable robustness advantageous for particular manufacturing operations.
  • diamond-like glass coatings show desirable expansion/stretching capabilities with marked flexibility, such properties being generally, continually further enhanced as the oxygen content approaches zero.
  • Micro-elastic-modulus of such coatings, as determined using a nanoindenter, is generally, favorably less than 11 GPa.
  • Oxygen-lean to oxygen- free diamond-like glass coatings include hydrogen and on a hydrogen free basis about 20 to about 40 atomic percent of silicon, greater than 39 atomic percent of carbon, and less than 33 down to and including zero atomic percent of oxygen.
  • diamond-like glass coatings contain on a hydrogen free basis from about 20 to about 40 atomic percent of silicon, greater than 42 atomic percent of carbon, less than 30 down to and including zero atomic percent of oxygen; more favorably from about 20 to about 40 atomic percent of silicon, greater than 45 atomic percent of carbon, less than 28 down to and including zero atomic percent of oxygen; even more favorably from about 20 to about 40 atomic percent of silicon, greater than 50 atomic percent of carbon, less than 25 down to and including zero atomic percent of oxygen; yet even more favorably from about 20 to about 40 atomic percent of silicon, greater than 50 atomic percent of carbon, less than 20 down to and including zero atomic percent of oxygen, and yet even further more favorably from about 20 to, but not including 40 atomic percent of silicon, greater than 60 atomic
  • the content of oxygen is zero up to and including about 12 atomic percent.
  • the content of silicon is in the range from about 20 to about 35 atomic percent.
  • “Hydrogen free basis” refers to the atomic composition of a material (i.e., in atomic percent) as established by a method such as X-ray photoelectron spectroscopy (XPS) which does not detect hydrogen even if large amounts are present in the coating.
  • XPS X-ray photoelectron spectroscopy
  • Diamond-like glass coatings described herein have relatively low intrinsic stress and thus excellent long-term adhesion and durability (unlike diamond-like carbon coatings which have a tendency to flake off due to relatively high intrinsic stress within the coating).
  • diamond- like glass coatings described herein are particularly advantageous as coatings on a surface or surfaces of a medicinal inhalation device component which undergoes movement in itself (e.g., a compression spring of a metered dose valve) or movement in conjunction with or relative to other components (e.g., a valve stem of a metered dose valve).
  • a medicinal inhalation device component which undergoes movement in itself (e.g., a compression spring of a metered dose valve) or movement in conjunction with or relative to other components (e.g., a valve stem of a metered dose valve).
  • Diamond-like glass coatings as well as methods of making diamond-like glass and apparatus for depositing diamond-like glass are described in U.S. Patent No. 6,696,157 (David et al) the content of which is incorporated here in its entirety.
  • plasma deposition under conditions of ion bombardment is distinct from plasma polymerization.
  • plasma polymerization polymerized species formed in the plasma deposit (as is) on the substrate to provide a polymer coating on the surface(s) of the substrate.
  • plasma deposition is carried out in such a manner that no ion sheath is formed (e.g., using conventional microwave or inductively coupled plasma systems) or the substrate to be coated with the polymer is positioned outside of any ion sheath, if at all formed.
  • the substrate is located in proximity to the grounded electrode or placed at a floating potential (i.e., electrically isolated and located outside of any ion sheath formed during RF -plasma deposition).
  • plasma deposition as used herein, unless otherwise specified, will be understood to be plasma deposition under conditions of ion bombardment.
  • plasma deposited as used herein, unless otherwise specified, will be understood to be plasma deposited under ion bombardment.
  • Forming a diamond-like glass coating as described herein by plasma deposition can be carried out in a suitable reaction chamber having a capacitively-coupled system with at least one electrode powered by an RF (radio frequency) source and at least one grounded electrode, such as those described in U.S. Patent Nos. 6,696,157 (David et al.) and 6,878,419 (David et al.).
  • RF radio frequency
  • Other apparatuses include those schematically illustrated and described in the co-pending application PCT/ US2008/082600.
  • an apparatus described in PCT/ US2008/ 082600 may include a grounded chamber (also acting here as a grounded electrode) from which air is removed by a pumping stack, where gas or gases to form the plasma are generally injected radially inwardly through the reactor wall to an exit pumping port in the center of the chamber.
  • a substrate to be coated typically a medicinal inhalation device component per se or alternatively a work-piece from which such a component may be subsequently formed or worked
  • a substrate or a plurality of substrates are tumbled during deposition, such tumbling favorably allowing for uniform deposition on the surfaces of the substrate(s).
  • the chamber is a tube, in particular a quartz tube, the ends of which are sealed with e.g., aluminum flanges, each flange typically provided with a port, one port being connected to a pumping stack and the other being connected to a gas supply system.
  • the ports together with the connecting-system are favorably configured and arranged to allow for rotation of the tube and thus the chamber during plasma deposition.
  • the RF-powdered electrode is configured as an arc conforming to the curvature of the tube and is positioned just underneath the tube but separated from the tube by a narrow gap.
  • the chamber is rotated so the substrate(s) to be coated tumble; tumbling can be desirably facilitated through the inclusion of baffles within the tube.
  • the substrate(s) to be coated will be found within the lower portion of the tube, and thus positioned in proximity of the RF -powered electrode so that the substrate(s) will be located within the ion sheath.
  • An additional system is described below in conjunction with the Examples.
  • the substrate Before plasma deposition, it is desirable to expose the substrate to an oxygen plasma or alternatively an argon plasma, more desirably an oxygen plasma. It is most desirable to expose the substrate to an oxygen plasma under conditions of ion bombardment (i.e., generating an ion sheath and having the substrate located within the ion sheath during said oxygen plasma treatment). Typically for this pre -treatment, power densities in the range from about 0.10 to about 0.95 watts/square cm can be applied.
  • flow densities (of the pre-treating gas, e.g., oxygen or argon) in the range from about 0.01 to about 1 sccm/square cm, preferably about 0.05 to 1 about sccm/square cm, most preferably, about 0.1 to about 0.6 sccm/square cm can be applied.
  • Power density is a ratio of the plasma power (typically in watts) and the surface area (typically in square cm) of the substrate to-be-coated (i.e., the density of plasma power at or upon the surface to-be-coated).
  • flow density is a ratio of the flow (typically in standard cubic centimeters per minute (seem)) of the gas in question and the surface area of the substrate to-be coated.
  • a solvent washing step with an organic solvent such as acetone or ethanol may also be included prior to the exposure to an oxygen or argon plasma as described above.
  • the plasma deposition system is evacuated to any extent necessary to remove air and any impurities.
  • a gas comprising one or more organosilicon is introduced into the system at a desired and/or needed flow rate.
  • the flow rates are selected so that a sufficient flow is provided to establish a suitable pressure at which to carry out plasma deposition.
  • the pressure at the surface to-be-coated is greater than 100 millitorr, in particular equal to or greater than 300 millitorr, more particularly in the range from 500 millitorr to 5000 millitorr.
  • the flow density of the organosilicon applied is greater than about 0.01 sccm/square cm, more favorably greater than about 0.05 sccm/square cm, most favorably greater than about 0.1 sccm/square cm.
  • flow densities are less than about 0.30 sccm/square cm, more favorably less than about 0.25 sccm/square cm.
  • Flow density of organosilicon refers to the organosilicon gas per se or if a mixture of organosilicon compounds is being used, the mixture of organosilicons (i.e., without any non-organosilicon assist gases, if used).
  • An RF electric field is applied to the powered electrode, ionizing the gas and establishing a plasma.
  • the plasma density is greater than about 0.10 watts/square cm. It has been found advantageous in facilitating the provision of flexible coatings, to apply lower power density in combination with longer deposition times.
  • energy is coupled into the plasma through electrons.
  • the plasma acts as the charge carrier between the electrodes.
  • the plasma is typically visible as a colored cloud.
  • the plasma also forms an ion sheath proximate at least to the RF -powered electrode. The ion sheath typically appears as a darker area around the electrode.
  • the depth of the ion sheath normally ranges from about 1 mm to about 50 mm and depends on factors such as the type and concentration of gas used, pressure, the spacing between the electrodes, and relative size of the electrodes. For example, reduced pressures will increase the size of the ion sheath. When the electrodes are different sizes, a larger, stronger ion sheath will form around the smaller electrode. Generally, the larger the difference in electrode size, the larger the difference in the size of the ion sheaths, and increasing the voltage across the ion sheath will increase ion bombardment energy.
  • plasma deposition comprises ionizing a gas comprising at least one organosilicon compound.
  • the silicon of the at least one organosilicon compound is present in an amount of at least about 5 atomic percent of the gas mixture.
  • the organosilicon comprises at least one of trimethylsilane, triethylsilane, trimethoxysilane, triethoxysilane, tetramethylsilane, tetraethylsilane, tetramethoxysilane, tetraethoxysilane, hexamethylcyclotrisiloxane, tetramethylcyclotetrasiloxane, tetraethylcyclotetrasiloxane, octamethylcyclotetrasiloxane, hexamethyldisiloxane, and bistrimethylsilylmethane. Tetramethylsilane and tetraethyoxysilane have been found to be particularly useful
  • the gas comprising an organosilicon may further comprise an additional gas or gases.
  • Each additional gas can be added separately or in combination with each other. If a gas is mixed along with the organosilicon compound(s), the atomic percent of silicon in the gas mixture generally is calculated based on the volumetric (or molar) flow rates of the component gases in the mixture.
  • the source gas may for example further comprise argon and/or hydrogen, in particular for plasma deposition under ion bombardment conditions.
  • the application of argon normally is not incorporated into the deposited coating) enhances ion bombardment, while the application of hydrogen promotes the formation of high packing density as well as provides an additional source of hydrogen.
  • the source gas may further comprise ammonia and/or nitrogen.
  • composition comprising an at least partially fluorinated compound comprising at least one silane group will be applied, it is desirable not to use ammonia and nitrogen gas, nor a sulfur containing gas.
  • the diamond- like glass coating is substantially free or free of amine functional groups and substantially free or free of amido functional groups as well as substantially free or free of thiol functional groups so as to minimize or avoid formation of silicon-nitrogen or silicon- sulfur bonds, said bonds having been determined to be undesirable in terms of durability and/or robustness of the coating system over the life of medicinal inhalation devices.
  • the non-metal/diamond-like glass coating is advantageously substantially free of nitrogen (e.g., at most about 5 atomic percent of nitrogen (on a hydrogen free basis)), in particular free of nitrogen.
  • the non-metal/diamond-like glass coating is advantageously substantially free of sulfur (e.g., at most about 1 atomic percent of sulfur (on a hydrogen free basis)), in particular free of sulfur.
  • the source gas may further comprise a source of fluorine e.g., carbon tetrafluoride.
  • fluorine e.g., carbon tetrafluoride.
  • the inclusion of fluorine has been determined to be generally undesirable in terms of structural integrity of the coating (in particular adhesion of the coating to the substrate surface as well as overall durability of the coating).
  • the non-metal/diamond-like glass coating is advantageously substantially free of fluorine (e.g., at most about 1 atomic percent of fluorine (on a hydrogen free basis)), in particular free of fluorine.
  • the source gas may further comprise oxygen gas e.g., as an assist gas.
  • oxygen gas e.g., as an assist gas.
  • the amount of oxygen gas is less than 35% on a molar basis, in particular less than 30% on a molar basis.
  • the source gas comprises oxygen gas and/or an organosilicon compound including oxygen atoms
  • the source gas is substantially free or free of an oxygen assist gas.
  • it is desirable that the source gas is substantially free or free of oxygen-containing organosilicons. (Substantially free means that the amount of oxygen assist gas or oxygen-containing organosilicon(s) is no more than that corresponding to 5% on an atomic basis of oxygen relative to total content of silicon on an atomic basis.)
  • Plasma deposition of the non-metal/diamond-like glass coating typically occurs at a rate ranging from about 1 to about 100 nm/second. The rate will depend on conditions including pressure, power, concentration of gas, types of gases, relative size of the electrodes, and so on. In general, the deposition rate increases with increasing power, pressure, and concentration of gas, although the rate can approach an upper limit. Desirably plasma deposition is carried out for a period of time such that the deposited diamond-like glass coating has a thickness in the range from about 5 nm to about 5000 nm.
  • non- metal/diamond-like glass coating having a thickness greater than 100 nm, more desirably a thickness equal to or greater than 250 nm, most desirably a thickness greater than 550 nm.
  • the non-metal/diamond-like glass coatings have a thickness equal to or less than 5000 nm, in particular a thickness equal to or less than 3500 nm, more particularly a thickness equal to or less than 2500 nm, most particularly a thickness equal to or less than 2000 nm.
  • diamond-like glass coating may be used alone, e.g., free of a fluorine-containing over-coating, in particular free of an over-coating.
  • methods of making a medicinal inhalation device or making a component of a medicinal inhalation device are favorably free of a step of applying a fluorine-containing over-coating, more favorably free of applying an over-coating, onto the surface of the diamond-like glass coating.
  • the coating may be desirably used in its native, deposited state.
  • the diamond-like glass coating may be subjected to a post surface treatment.
  • a post surface treatment is performed, desirably such treatment does not substantially increase the surface energy of the deposited coating and/or generate reactive groups on the surface of the deposited coating.
  • at least a portion of a surface of the formed non-metal/diamond-like glass coating may be exposed to fluorine- containing-gas plasma, under ion bombardment conditions.
  • the fluorine-containing-gas- plasma may favorably comprise a fluorine-containing compound selected from the group consisting of fluorine (F 2 ); nitrogentrifluoride (NF 3 ); sulfurhexafluoride (SF 6 ); silicontetrafluorine (SiF 4 ); phosphorustrifluoride (PF3); carbon tetrafluoride (CF 4 ); perfluoroethane (C 2 F 6 ); perfluoropropane (C3F8), perfluorobutane (C 4 F 1 O) and perfluoropentane (CsF 12 ) and their isomeric forms; hexafluoropropylene (HFP) trimer; 2,2,3-trifluoro-3-(trifluoromethyl)oxirane (CsF 6 O); and mixtures thereof.
  • fluorine fluorine
  • NF 3 nitrogentrifluoride
  • SF 6 sulfurhexafluoride
  • SiF 4 silicontetrafluorine
  • HFP trimer hexafluoropropylene (HFP) trimer
  • HFP hexafluoropropylene
  • a composition comprising an at least partially fluorinated compound may be advantageously applied to at least a portion of a surface of the non-metal/diamond-like glass coating (preferably to the entire surface of the formed non-metal/diamond-like glass coating).
  • the at least partially fluorinated compound comprises at least one functional group.
  • the non-metal/diamond-like glass coating comprises at least one functional group, where the at least one functional group is capable of forming a covalent bond with the at least one functional group of the at least partially fluorinated compound.
  • the term "at least one functional group” as used herein is to be generally understood to include as a preferred embodiment "a plurality of functional groups”.
  • the at least one functional group of the non-metal/diamond-like glass coating desirably includes an active hydrogen.
  • the at least one functional group may be a hydroxyl group (-OH), a thiol group (-SH), an amine group (-NH- or -NH 2 ), a carboxyl group (-COOH), an amide group (-C0NH- or -CONH 2 ) or a mixture of such groups; favorably a hydroxyl group, a carboxyl group or a mixture of such groups; and more favorably a hydroxyl group.
  • the non-metal/diamond-like glass coating may be provided with the at least one functional group upon its formation through plasma deposition under ion bombardment conditions, or alternatively (and more favorably) the coating already plasma deposited under ion bombardment conditions, may be provided with the at least one functional group through a subsequent treatment.
  • such coatings allow for the provision of a dense distribution and high number of functional groups, such as functional groups having an active hydrogen (e.g., hydroxyl groups (-OH) and/or carboxyl groups (-C00H), in particular hydroxyl groups) for subsequent bonding upon application of said composition comprising at least partially fluorinated compound comprising an at least one functional group.
  • functional groups having an active hydrogen e.g., hydroxyl groups (-OH) and/or carboxyl groups (-C00H), in particular hydroxyl groups
  • the surface of the non-metal/diamond like-glass coating is exposed to an oxygen plasma and/or water vapor, more favorably exposed to an oxygen plasma and/or water vapor under ion bombardment conditions (for example in order to form or to form additional silanol groups on the surface).
  • a treatment (depending on the particular composition of the non-metal/diamond-like glass coating) generally advantageously allows for the provision of a coating with at least one functional group.
  • pressures at the surface are typically maintained between 10 mTorr (1.4 Pa) and 2000 mTorr (286 Pa)
  • oxygen flow density is greater than 0.1 sccm/square cm
  • power density is greater than 0.1 watts/square cm.
  • the non-metal/diamond-like glass coating may be favorably exposed to a corona treatment prior to applying the composition comprising the at least partially fluorinated compound comprising at least one functional group.
  • the at least partially fluorinated compound includes a polyfluoropolyether segment, preferably a perfluorinated polyfluoropolyether segment, for enhanced surface properties as well as enhanced coating efficiency and structural integrity.
  • a polyfluoropolyether segment including perfluorinated repeating units including short chains of carbon, where desirably the number of carbon atoms in sequence is at most 6, more desirably at most 4, even more desirably at most 3, and most desirably at most 2, facilitates durability/flexibility of the applied fluorine-containing coating as well as minimizing a potential of bioaccumulation of perfluorinated moieties.
  • the at least one functional group of the at least partially fluorinated compound includes a hydrolyzable group (e.g., hydrolyzable in the presence of water, optionally under acidic or basic conditions producing groups capable of undergoing a condensation reaction (for example silanol groups)).
  • a hydrolyzable group e.g., hydrolyzable in the presence of water, optionally under acidic or basic conditions producing groups capable of undergoing a condensation reaction (for example silanol groups)).
  • the at least one functional group of the at least partially fluorinated compound is a silane group.
  • the silane group includes at least one hydrolyzable group, more favorably at least two hydrolyzable groups, and most favorably three hydrolyzable groups.
  • the hydrolyzable groups may be the same or different.
  • a hydrolyzable group is a group selected from the group consisting of hydrogen, halogen, alkoxy, acyloxy, aryloxy, and polyalkyleneoxy, more desirably a group selected from the group consisting of alkoxy, acyloxy, aryloxy, and polyalkyleneoxy, even more desirably a group selected from the group consisting of alkoxy, acyloxy and aryloxy, and most desirably an alkoxy group (e.g., OR' wherein each R' is independently a C 1-6 alkyl, in particular a C 1-4 alkyl).
  • the at least partially fluorinated compound comprising at least one functional group is a polyfluoropolyether silane, more desirably a multifunctional polyfluoropolyether silane, and most desirably a difunctional polyfluoropolyethersilane.
  • compositions comprises a multifunctional polyfluoropolyether silane (in particular a difunctional polyfluoropolyethersilane) and a monofunctional polyfluoropolyethersilane is particularly favorable.
  • multifunctional polyfluoropolyether silane as used herein is generally understood to mean a multivalent polyfluoropolyether segment functionalized with a multiple of functional silane groups
  • difunctional polyfluoropolyether silane as used herein is generally understood to mean a divalent polyfluoropolyether segment functionalized with a multiple of functional silane groups (in particular two to four functional silane groups, more particularly two functional silane groups).
  • monofunctional polyfluoropolyether silane as used herein is generally understood to mean a monovalent polyfluoropolyether segment functionalized with one or more functional silane groups (in particular one functional silane group or two functional silane groups).
  • a multifunctional polyfluoropolyether silane in particular a difunctional polyfluorpolyether silane, allows for high application efficiency and coverage as well as extensive bonding (covalent bonding) to the diamond-like glass coating as well as cross-linking within the fluorine containing coating itself thus facilitating structural integrity of the applied fluorine-containing coating.
  • a multifunctional polyfluoropolyether silane in conjunction with a monofunctional polyfluoropolyether silane provides in addition highly desirable surface characteristics.
  • polyfluoropolyether segment(s) is (are) not linked to silane group(s) via a functionality that includes a nitrogen-silicon bond or a sulfur-silicon bond.
  • polyfluoropolyether segment(s) is (are) linked to silane group(s) via a functionality that includes a carbon-silicon bond, more particularly via a -C(R) 2 -Si functionality where R is independently hydrogen or a C 1-4 alkyl group (preferably hydrogen), and most particularly, via a -(C(R) 2 VC(R) 2 -Si functionality where k is at least 2 (preferably 2 to about 25, more preferably 2 to about 15, most preferably 2 to about 10).
  • k is at least 2
  • k is at least 2 advantageously, additionally provides flexural strength
  • the at least partially fluorinated compound comprising at least one silane group is a polyfluoropolyether silane of the Formula Ia:
  • Q is an organic divalent or trivalent linking group; each R is independently hydrogen or a C 1-4 alkyl group; each Y is independently a hydrolyzable group;
  • R la is a Ci_8 alkyl or phenyl group; x is 0 or 1 or 2; y is 1 or 2; and z is 1, 2, 3, or 4.
  • polyfluoropoly ether silanes in accordance with Formula Ia favorably allows the provision of medicinal inhalation devices or components thereof comprising a non-metal/diamond-like glass coating on at least a portion of surface of the device or component, as applicable, and a polyfluoropoly ether-containing coating bonded to the non-metal/diamond-like glass coating, wherein the polyfluoropolyether-containing coating comprises polyfluoropoly ether silane entities of the following Formula Ib:
  • R/ is a monovalent or multivalent polyfluoropolyether segment
  • Q is an organic divalent or trivalent linking group
  • each R is independently hydrogen or a C 1-4 alkyl group
  • R la is a C 1 -S alkyl or phenyl group
  • x is 0 or 1 or 2
  • y is 1 or 2
  • z is 1, 2, 3, or 4.
  • the at least one covalent bond shared with the non-metal/diamond-like glass coating is a bond to an oxygen atom in Si(O-)3_ x .
  • such polyfluoropolyether-containing coatings are typically transparent or translucent.
  • the monovalent or multivalent polyfluoropolyether segment, R/ includes linear, branched, and/or cyclic structures, that may be saturated or unsaturated, and includes two or more in- chain oxygen atoms.
  • R/ is preferably a perfluorinated group (i.e., all C-H bonds are replaced by C-F bonds).
  • hydrogen atoms may be present instead of fluorine atoms provided that not more than one atom of hydrogen is present for every two carbon atoms.
  • R/ includes at least one perfluoromethyl group.
  • the monovalent or multivalent polyfluoropolyether segment, R / comprises perfluorinated repeating units selected from the group consisting Of -(C n F 2n )-, - (C n F 2n O)-, -(CF(Z))-, -(CF(Z)O)-, -(CF(Z)C n F 2n O)-, -(C n F 2n CF(Z)O)-, -(CF 2 CF(Z)O)-, and combinations thereof; wherein n is an integer from 1 to 6; Z is a perfluoroalkyl group, an oxygen-containing perfluoroalkyl group, a perfluoroalkoxy group, or an oxygen- substituted perfluoroalkoxy group, each of which can be linear, branched, or cyclic, and have 1 to 5 carbon atoms and up to 4 oxygen atoms when oxygen-containing or oxygen- substituted.
  • the total number of carbon atoms in sequence per unit is at most 6 (more desirably at most 4, and most desirably at most 3). Being oligomeric or polymeric in nature, these compounds exist as mixtures and are suitable for use as such.
  • the perfluorinated repeating units may be arranged randomly, in blocks, or in an alternating sequence.
  • the polyfluoropolyether segment comprises perfluorinated repeating units selected from the group consisting Of -(C n F 2n O)-, -(CF(Z)O)-, -(CF(Z)C n F 2n O)-, -(C n F 2n CF(Z)O)-, -(CF 2 CF(Z)O)-, and combinations thereof; and more favorably perfluorinated repeating units selected from the group consisting Of -(C n F 2n O)-, -(CF(Z)O)-, and combinations thereof.
  • n is an integer from 1 to 4; or 1 to 3; or 1 or 2.
  • Z is a -CF 3 group.
  • R/ is monovalent, and z is 1.
  • R/ is terminated with a group selected from the group consisting Of C n F 2n+1 -, C n F 2n+1 O-, and X'C n F 2n O- wherein X' is a hydrogen.
  • the terminal group is C n F 2n+1 - or C n F 2n+1 O- wherein n is an integer from 1 to 6 or 1 to 3.
  • Rf is preferably multivalent and z is 2, 3 or 4, more preferably R/ is divalent, and z is 2.
  • the approximate average structure of R/ is selected from the group consisting of -CF 2 O(CF 2 O) m (C 2 F 4 O) p CF 2 -, -CF 2 O(C 2 F 4 O) P CF 2 -, -CF(CF 3 )O(CF(CF 3 )CF 2 O) P CF(CF 3 )-, -(CF 2 ) 3 O(C 4 F 8 O) P (CF 2 ) 3 -, -CF(CF 3 )-(OCF 2 CF(CF 3 )) p O-C,F 2 ,-O(CF(CF 3 )CF 2 ⁇ ) p CF(CF 3 )- (wherein t is 2 to 4), and wherein m is 1 to 50, and p is 3 to 40.
  • R/ is selected from the group consisting Of -CF 2 O(CF 2 O) 1n (C 2 F 4 O) P CF 2 -, -CF 2 O(C 2 F 4 O) P CF 2 -, and -CF(CF 3 )-(OCF 2 CF(CF 3 )) p O-(C,F 2 ,)-O(CF(CF 3 )CF 2 ⁇ ) p CF(CF 3 )-, and wherein t is 2, 3 or 4, and the average value of m+p or p+p or p is from about 4 to about 24.
  • polyfluoro- polyether silanes such as those described above, also typically include a distribution of oligomers and/or polymers, so p and/or m may be non-integral and where the number is the approximate average over this distribution.
  • the organic divalent or trivalent linking group, Q can include linear, branched, or cyclic structures that may be saturated or unsaturated.
  • the organic divalent or trivalent linking group, Q optionally contains one or more heteroatoms selected from the group consisting of sulfur, oxygen, and nitrogen, and/or optionally contains one or more functional groups selected from the group consisting of esters, amides, sulfonamides, carbonyl, carbonates, ureylenes, and carbamates.
  • Q favorably includes a segment with not less than 2 carbon atoms, said segment of Q being directly bonded to the -C(R) 2 - group of the silane-containing moiety (i.e., for Formula Ia -C(R) 2 -Si(Y) 3 _ x (R la ) x and for Formula Ib -C(R) 2 -Si(O-) 3 _ x (R la ) x ).
  • Q includes not more than about 25 carbon atoms.
  • Q is preferably substantially stable against hydrolysis and other chemical transformations, such as nucleophilic attack. When more than one Q group is present, the Q groups can be the same or different.
  • Q includes organic linking groups such as -C(O)N(R)-(CH 2 ) k -, -S(O) 2 N(R)-(CH 2 V, -(CH 2 ) k -,
  • Q is a divalent linking group, and y is 1.
  • Q is favorably a saturated or unsaturated hydrocarbon group including 1 to about 15 carbon atoms and optionally containing 1 to 4 heteroatoms and/or 1 to 4 functional groups.
  • Q is a linear hydrocarbon containing 1 to about 10 carbon atoms, optionally containing 1 to 4 heteroatoms and/or 1 to 4 functional groups.
  • Q contains one functional group.
  • Q is preferably -C(O)N(R)(CH 2 V, -OC(O)N(R)(CH 2 V, -CH 2 O(CH 2 V, or -CH 2 -OC(O)N(R)-(CH 2 V, wherein R is hydrogen or C 1-4 alkyl.
  • R is hydrogen
  • the hydrolyzable groups, Y, of Formula Ia may be the same or different and are capable of hydrolyzing, for example, in the presence of water, optionally under acidic or basic conditions, producing groups capable of undergoing a condensation reaction, for example silanol groups.
  • groups capable of undergoing a condensation reaction for example silanol groups.
  • methoxy and ethoxy groups form essentially immediately "in situ" (e.g., in the presence of water) hydroxy groups, so that silanol groups are generated.
  • each Y of Formula Ia is independently a group selected from the group consisting of hydrogen, halogen, alkoxy, acyloxy, aryloxy, and polyalkyleneoxy, more desirably each Y is independently a group selected from the group consisting of alkoxy, acyloxy, aryloxy, and polyalkyleneoxy, even more desirably each Y is independently a group selected from the group consisting of alkoxy, acyloxy and aryloxy, and most desirably each Y is independently an alkoxy group.
  • alkoxy is -OR'
  • acyloxy is -OC(O)R', wherein each R is independently a lower alkyl group, optionally substituted by one or more halogen atoms.
  • R' is preferably C 1-6 alkyl and more preferably Ci_ 4 alkyl.
  • R' can be a linear or branched alkyl group.
  • aryloxy is -OR" wherein R" is aryl optionally substituted by one or more substituents independently selected from halogen atoms and C 1-4 alkyl optionally substituted by one or more halogen atoms.
  • R" is preferably unsubstituted or substituted C 6-12 aryl and more preferably unsubstituted or substituted C 6-10 aryl.
  • polyalkyleneoxy is -O-(CHR 4 -CH 2 O) q -R 3 wherein R 3 is C 1-4 alkyl, R 4 is hydrogen or methyl, with at least 70% of R 4 being hydrogen, and q is 1 to 40, preferably 2 to 10.
  • x is 0.
  • R/ is -CF 2 O(CF 2 O) I i 1 (C 2 F 4 O) P CF 2 - and Q-
  • C(R) 2 -Si(Y) 3 - ⁇ (R la ) ⁇ is C(O)NH(CH 2 ) 3 Si(OR')3, in particular wherein R' is methyl or ethyl.
  • R/ is -CF 2 O(CF 2 O) m (C 2 F 4 O) p CF 2 - and Q-C(R) 2 -Si(O-) 3 - x (R la ) x is C(O)NH(CH 2 )3Si(O-)3.
  • m+p or p is from about 4 to about 24, more particularly m and p are each about 9 to aboutl2.
  • R/ is C 3 F 7 O(CF(CF 3 )CF 2 ⁇ ) p CF(CF 3 )-, and Q- C(R) 2 -Si(Y') 3 -x(R la )x is C(O)NH(CH 2 )SSi(OR) 3 , in particular wherein R' is methyl or ethyl.
  • R/ is C 3 F 7 O(CF(CF 3 )CF 2 O) P CF(CF 3 )- and Q-C(R) 2 -
  • x (R la ) x is C(O)NH(CH 2 ) 3 Si(O-) 3 .
  • p is from about 3 to about 20, more particularly from about 4 to about 10.
  • the composition advantageously comprises at least the following two polyfluoropolyether silanes in accordance with Formula Ia: (a) a first polyfluoropolyether silane wherein R/ is C 3 F 7 O(CF(CF 3 )CF 2 O) P CF(CF 3 )-, and Q-C(R) 2 -Si(Y') 3 -x(R la )x is C(O)NH(CH 2 ) 3 Si(OR') 3 (in particular wherein R is methyl or ethyl) wherein p is 3 to 50, in particular wherein p is from about 3 to about 20, more particularly p is from about 4 to about 10; and
  • a second polyfluoropolyether silane wherein R/ is -CF 2 O(CF 2 O) m (C 2 F 4 O) p CF 2 -, and Q-C(R) 2 -Si(Y') 3 .
  • x (R la ) x is C(O)NH(CH 2 ) 3 Si(OR') 3 , (in particular wherein R' is methyl or ethyl) wherein m is 1 to 50 and p is 3 to 40, in particular wherein the average value of m+p or p is from about 4 to about 24, more particularly wherein m and p are each about 9 to about 12.
  • the composition comprises a catalyst and the composition comprises at least a total of 0.1 wt % of said first and second polyfluoropolyether silanes, in particular at least a total of 0.5 wt % of said first and second polyfluoropolyether silanes, more particularly at least a total of one (1) wt % of said first and second polyfluoropolyether silanes.
  • the composition is free of catalyst and the composition comprises at least a total of one (1) wt % of said first and second polyfluoropoly ether silanes, in particular at least a total of 2.5 wt % of said first and second polyfluoropolyether silanes, more particularly at least a total of 5 wt % of said first and second polyfluoropolyether silanes.
  • the weight percent ratio of the first to second polyfluoropolyether silane (first polyfluoropolyether silane : second polyfluoropolyether silane) in the composition is equal to or greater than 10 : 90, in particular equal to or greater than 20 : 80, more particularly equal to or greater than 30 : 70, most particularly equal to or greater than 40 : 60.
  • the weight percent ratio of the first to second polyfluoropolyether silane (first polyfluoropolyether silane : second polyfluoropolyether silane) in the composition is equal to or less than 99 : 1, in particular equal to or less than 97 : 3, most particularly equal to or less than 95 : 5.
  • the weight average molecular weight of the polyfluoropolyether segment is about 900 or higher, more desirably about 1000 or higher. Higher weight average molecular weights further facilitate durability as well as minimizing a potential of bioaccumulation.
  • the weight average molecular weight of the polyfluoropolyether segment is desirably about 6000 at most and more desirably about 4000 at most, most desirably about 3000 at most.
  • Polyfluoropolyether silanes typically include a distribution of oligomers and/or polymers. Desirably for facilitation of the structural integrity of the polyfluoropolyether-containing coating as well as minimization of a potential of bioaccumulation, the amount of polyfluoropolyether silane (in such a distribution) having a polyfluoropolyether segment having a weight average molecular weight less than 750 is not more than 10% by weight (more desirably not more than 5 % by weight, and even more desirably not more 1% by weight and most desirably 0%) of total amount of polyfluoropolyether silane in said distribution.
  • the composition comprising an at least partially fluorinated compound comprising at least one functional group further includes an organic solvent.
  • the polyfluoropolyether silane is desirably applied as a composition comprising the polyfluoropolyether silane and an organic solvent.
  • the organic solvent or blend of organic solvents used typically is capable of dissolving at least about 0.01 percent by weight of the polyfluoropolyether silane, in particular one or more silanes of the Formula Ia. It is desirable that the solvent or mixture of solvents have a solubility for water of at least about 0.1 percent by weight, and for certain of these embodiments, a solubility for acid of at least about 0.01 percent by weight.
  • Suitable organic solvents, or mixtures of solvents can be selected from aliphatic alcohols, such as methanol, ethanol, and isopropanol; ketones such as acetone and methyl ethyl ketone; esters such as ethyl acetate and methyl formate; ethers such as diethyl ether, diisopropyl ether, methyl t-butyl ether and dipropyleneglycol monomethylether (DPM); hydrocarbon solvents such as alkanes, for example, heptane, decane, and paraffmic solvents; fluorinated hydrocarbons such as perfluorohexane and perfluorooctane; partially fluorinated hydrocarbons, such as pentafluorobutane; hydrofluoroethers such as methyl perfluorobutyl ether and ethyl perfluorobutyl ether.
  • ketones such as acetone and methyl ethy
  • the organic solvent is a fluorinated solvent, which includes fluorinated hydrocarbons, partially fluorinated hydrocarbons, and hydrofluoroethers.
  • the fluorinated solvent is a hydrofluoroether.
  • the hydrofluoroether is methyl perfluorobutyl ether and/or ethyl perfluorobutyl ether.
  • the organic solvent is a lower alcohol.
  • the lower alcohol is selected from the group consisting of methanol, ethanol, isopropanol, and mixtures thereof.
  • the lower alcohol is ethanol.
  • the composition favorably further comprises an acid.
  • the acid is selected from the group consisting of acetic acid, citric acid, formic acid, triflic acid, perfluorobutyric acid, sulfuric acid, and hydrochloric acid.
  • the acid is hydrochloric acid.
  • composition comprising an at least partially fluorinated compound comprising at least one functional group may favorably further comprise a non-fluorinated cross-linking agent that is capable of engaging in a cross-linking reaction.
  • a cross-linking agent comprises one or more non-fluorinated compounds, each compound having at least two hydrolyzable groups.
  • a cross-linking agent comprises one or more non-fluorinated compounds of silicon having at least two hydrolyzable groups per molecule.
  • the hydrolyzable groups are directly bonded to the silicon in accordance to Formula II:
  • R 5 represents a non-hydrolyzable group
  • Y 2 represents a hydrolyzable group
  • g is 0, 1 or 2.
  • the non-hydrolyzable group R 5 is generally not capable of hydrolyzing under the conditions used during application of the composition comprising the at least partially fluorinated compound comprising at least one functional group.
  • the non- hydrolyzable group R 5 may be independently selected from a hydrocarbon group. If g is 2, the non-hydrolyzable groups may the same or different. Preferably g is 0 or 1, more preferably g is 0.
  • the hydrolyzable groups Y 2 may be the same or different and are generally capable of hydrolyzing under appropriate conditions, for example under acidic or basic aqueous conditions, such that the cross-linking agent can undergo condensation reactions. Preferably, the hydrolyzable groups upon hydrolysis yield groups, such as silanol groups capable of undergoing condensation reactions. Typical and preferred examples of hydrolyzable groups include those as described with respect to Formula Ia.
  • Y 2 is an alkoxy, -OR 6 , more preferably an alkoxy where R 6 is a C 1-4 alkyl.
  • Non-fluorinated silicon compounds for use in a cross-linking agent include tetramethoxysilane, tetraethoxysilane, tetrapropoxysilane, tetrabutoxysilane, methyl triethoxysilane, dimethyldiethoxysilane, octadecyltriethoxy- silane, 3-glycidoxypropyltriethoxysilane, 3-aminopropyltrimethoxysilane, 3-aminopropyl- triethoxysilane, 3-trimethoxysilylpropylmethacrylate and mixtures thereof.
  • the cross-linking agent comprises C 1 -C 4 tetra-alkoxy derivatives of silicon, more preferably the cross-linking agent comprises tetraethoxysilane.
  • the amounts by weight of the at least partially fluorinated compound to the non- fluorinated cross-linking agent can change from about 10: 1 to about 1 :100, preferably from about 1 : 1 to about 1 :50 and most preferably from about 1 :2 to about 1 :20.
  • compositions including a hydrolyzable group may further comprise water.
  • composition comprising an at least partially fluorinated compound comprising at least one functional group (in particular one silane group), including any one of the above embodiments, can be applied to at least a portion of the surface (preferably the entire surface) of the non-metal/diamond-like glass coating using a variety of coating methods.
  • coating methods include but are not limited to spraying, dipping, spin coating, rolling, brushing, spreading and flow coating.
  • Preferred methods for application include spraying and dipping.
  • the composition comprising an at least partially fluorinated compound comprising at least one functional group in any one of its above described embodiments, is applied by dipping at least a portion of the substrate upon which the non-metal/diamond-like glass coating has been formed in said composition.
  • the composition comprising the at least partially fluorinated compound comprising at least one functional group is applied by spraying at least a portion of the substrate upon which the non-metal/diamond-like glass coating has been formed with said composition.
  • the diamond-like glass coating includes active functional groups on its surface, such as -SiOH (either provided during its forming or, more favorably and typically, via a post-treatment as described above) so that upon application of the composition comprising an at least partially fluorinated compound comprising at least one silane group (in particular a polyfluoropolyether silane or more particularly any one of the embodiments of Formula Ia) an extremely durable coating is formed through the formation of covalent bonds, including bonds in Si-O-Si groups.
  • the fluorine-containing coating is covalently bonded to the diamond-like glass coating through a plurality of covalent bonds, more favorably through covalent bonds including bonds in O-Si groups, more desirably including bonds in Si-O-Si groups
  • sufficient water should be present to cause hydrolysis of the hydrolyzable groups described above so that condensation to form Si-O- Si groups takes place, and thereby curing takes place.
  • the water can be present either in the treating composition or adsorbed to the substrate surface, for example.
  • sufficient water is present for the preparation of a durable coating if the application is carried out at room temperature in an atmosphere containing water, for example, an atmosphere having a relative humidity of about 30% to about 80%.
  • Application is typically carried out by contacting the substrate with the treating composition, generally at room temperature (typically about 20 0 C to about 25°C).
  • the treating composition can be applied to a substrate that is pre-heated at a temperature of for example between 60°Cand 150 0 C.
  • the treated substrate can be dried and cured at ambient temperature or (preferably) at elevated temperatures (e.g., at 40 0 C to 300 0 C), and for a time sufficient to dry and cure.
  • the treating composition may further comprise a thermal initiator.
  • the treated substrate may be cured (again if desired or needed) by irradiation (e.g., means of UV-irradiators, etc.).
  • the treating composition typically further comprises a photo- initiator, and curing is performed in a manner known per se, depending on the type and presence, respectively of the photo-initiator used in the treating composition.
  • a post-treatment process may include a rinsing step (e.g., before or after drying/curing, as desired or needed) to remove excess material, followed by a drying step.
  • a rinsing step e.g., before or after drying/curing, as desired or needed
  • the thickness of the fluorine-containing coating is favorably greater than a monolayer and thus is greater than 15 Angstroms.
  • the thickness of the fluorine-containing coating is at least about 2 nm, preferably at least about 10 nm, even more preferably at least about 25 nm, and most preferably at least about 40 nm.
  • the thickness is at most about 200 nm, preferably at most about 150 nm, and most preferably at most about 100 nm.
  • the combined thickness of the two coats may be about 100 nm up to about 5200 nm.
  • the combined thickness of the two coats is about 252 nm or higher, more favorably greater than about 552 nm.
  • the combined thickness of the two coats is about 3700 nm or lower, more favorably about 2700 nm or lower, most favorably about 2200 nm or lower.
  • Additional aspects of the present invention include: devices and components made in accordance with aforesaid methods.
  • methods of providing such medicinal inhalation devices and components as described herein are advantageous in their versatility and/or broad applicability to making various components of such medicinal inhalation devices, such components having significantly differing shapes and forms made of significantly differing materials.
  • methods described herein can be advantageously used to provide a coating on at least a portion of the interior surface (preferably on the entire interior surface, more preferably the entire surface) of an MDI aerosol container, in particular a conventional MDI aerosol container made of aluminum or an aluminum alloy as well as MDI aerosol containers made of other metals, such as stainless steel, as well as other materials such as glass, ceramic, plastics.
  • Methods described herein and/or the application of diamond- like glass coatings described herein may allow for the provision of plastic aerosol containers having favorable properties for commercial use.
  • Methods described herein can also be advantageously used to provide a coating on at least a portion of a surface (preferably the entire surface) of a valve stem or a valve body, in particular a valve stem or a valve body made of a polymer such as PBT or acetal.
  • particular embodiments in particular those embodiments including a diamond-like glass coating either alone or treated with a fluorine-containing plasma gas or over-coated with a fluorine-containing coating as described herein
  • coatings are particular advantageous for use with DPI powder containers or carriers or MDI aerosol containers.
  • such coatings allow the use of containers, e.g., MDI aerosol containers, made of plastic or other materials which in the past have been ruled out due to the potential of permeation of moisture from outside to the inside, permeation of aerosol formulation through or into the container material and/or extraction of container material into the aerosol formulation.
  • such coatings described herein that are transparent or translucent can be used to provide a transparent or translucent plastic MDI aerosol container which can be advantageous in that a patient can easily monitor the content of the container (i.e., whether it is empty and needs to be replaced).
  • Methods described herein can also be used to provide other medicinal inhalation devices including nebulizers, pump spray devices, nasal pumps, non-pressurized actuators or components of such devices. Accordingly medicinal inhalation devices or components described herein may also be nebulizers, pump spray devices, nasal pumps, non- pressurized actuators or components of such devices.
  • Methods described herein can also be used to provide other components used in medicinal inhalation such as breath-actuating devices, breath-coordinating devices, spacers, dose counters, or individual components of such devices, spacers and counters, respectively.
  • components described herein may also be breath-actuating devices, breath- coordinating devices, spacers, dose counters, or individual components of such devices, spacers, counters, respectively.
  • breath-actuating devices breath-coordinating devices
  • spacers spacers
  • dose counters individual components of such devices, spacers, counters, respectively.
  • the provision of such a coating on a component or components (in particular movable component(s) and/or component(s) in contact with a movable component) of a dose counter provides dry lubricity facilitating smooth operation of the dose counter.
  • Plasma treatment as described in the following was performed unless specified otherwise
  • Exemplary containers were treated in a custom-built system.
  • the system includes an aluminum manifold having two generally horizontal chambers, one connected to a gas feed/supply system and the other to a vacuum system, and a central vertical opening with appropriate seal systems to allow for sealing-connection to a nozzle; and an insulating barrier block made of polymeric material, polyetherimide, (available under the trademark ULTEM (grade 1000) of General Electric Company and available from many suppliers worldwide) having a central vertical opening and fitted below the manifold so that the openings were aligned.
  • polyetherimide available under the trademark ULTEM (grade 1000) of General Electric Company and available from many suppliers worldwide
  • the system includes a nozzle having five substantially parallel bores, a central bore and four outer bores, where the nozzle has a middle body-portion and two extensions on opposite ends, and the central bore runs through the extensions and body-portions and the outer bores run through the body-portion.
  • One end of the nozzle is inserted through the insulating barrier block into the manifold so that the respective opening of the central bore taps into the gas feed chamber and the respective openings of the outer bores tap into the vacuum chamber.
  • the body-portion of the nozzle is sealed within the barrier block, such that the lower surface of the body-portion and the openings of the outer bores are substantially flush with the lower surface of the barrier block and the central bore-extension extends beyond the lower surface of the body-portion of the nozzle (and the barrier block) about 44.45 mm.
  • a sealing system is provided on the lower side of the block near the block/nozzle conjunction to allow for a sealing-connection to the container to be coated. The system is fitted with four such nozzles.
  • the four nozzles were lowered into four containers so that the upper edge of the brim of each container was in contact with the lower side of the nozzle-body-portion and so that a seal was created between each container (outer surface of brim) and the outer lower surface of the barrier block. Voltage was applied to the containers and the nozzles were grounded to create the plasma and an ion sheath within the interior of the container, in order to coat the interior of the containers.
  • the containers were continuously evacuated via the outer bores (inlet openings near the brim) while gas was supplied into the containers via the central bore-extension.
  • Plasma was powered by a 1 kW, 13.56 MHz solid-state generator (Seren, Model No.
  • RlOOl available from Seren IPS, Inc., Vineland, New Jersey, USA
  • Rf Plasma Products Model AMN-IO available from Advanced Energy, Fort Collins, CO
  • the system had a nominal base pressure of 5 mTorr (0.67 Pa).
  • the flow rates of gases were controlled by flow controllers available from MKS Instruments Incorporated (Wilmington, MA).
  • the plasma treatment included the following steps:
  • Step 1 Exemplary containers were first treated in an oxygen plasma by flowing oxygen gas (99.99%, UHP Grade, available from Scott Specialty Gases, Plumsteadville, PA) at 50 standard cubic centimeters per minute (seem) flow rate while maintaining within the containers a pressure within the range of 1000-1500 millitorr (mtorr) (130-200 Pascals (Pa)) and plasma power of 75 watts.
  • oxygen gas 99.99%, UHP Grade, available from Scott Specialty Gases, Plumsteadville, PA
  • seem standard cubic centimeters per minute
  • the oxygen priming step was carried out for 20 seconds.
  • Step 2 Following the oxygen plasma priming, either oxygen flow was stopped ("0 seem")
  • Example 1 oxygen flow was maintained at a reduced flow of 5 seem, 10 seem, 15 seem or 20 seem (Examples 2 through 5, respectively) , and tetramethylsilane (99.9%, NMR Grade, available from Sigma-Aldrich Chemicals, St. Louis, MO) was introduced at a flow rate of 25 seem.
  • the pressure was held within the containers within the range of 600-1000 mtorr (80-130 Pa), and plasma power was held at 75 watts.
  • the treatment time was 180 seconds, with a corresponding deposition rate of about 100-300 nm/min.
  • Step 2 used in each case a TMS flow density of about 0.16 sccm/square cm.
  • XPS survey spectra were recorded at randomly selected areas on the plasma-treated substrate (such as areas on the interior surface of each plasma-treated aerosol container). Said XPS data were acquired and analyzed using a Kratos Model AXIS Ultra DLD spectrometer (available Kratos Analytical Ltd, Wharfside, Manchester, UK) (Hybrid Operation mode) with a monochromatic Al-K X-ray source and using Hybrid operation mode. The emitted photoelectrons were detected at a 90 degree take-off angle (take-off angle defining the angle between the sample surface and the axis of the XPS analyzer lens) with respect to the sample surface. A low-energy electron flood gun was used to minimize surface charging.
  • the area analyzed for each data point was approximately 700 ⁇ m x 300 ⁇ m. Pass energy for survey scan was 160 eV; scan rate 400 meV/Step; dwell time 87 ms. Three to four areas on each sample were analyzed and averaged to obtain the reported atomic % values.
  • aqueous copper sulfate pentahydrate/hydrochloric acid solution was prepared by combining 78 g of copper(II) sulfate pentahydrate, 20 mL of 37% hydrochloric acid, and 500 mL of deionized water.
  • a plurality of cans (up to 5) was examined and the reported score is the average of the scores.
  • Table 1 summarizes the results of the corrosion examination together with the-on- hydrogen- free-basis atomic percents of oxygen, silicon and carbon of Examples 1 to 5.
  • Containers coated using "0 seem” oxygen in step 2 were measured to have a surface energy of 28 dynes/cm using a dyne fluid.
  • Containers were coated as specified in the aforesaid plasma treatment method, with the following exceptions: in each case Step 1 (pre-treatment with oxygen) was conducted using a plasma power 50 watts; in each case in Step 2 oxygen flow was stopped ("0 seem"); and in Examples 7 and 8 the treatment time in Step 2 was 4 minutes or 5 minutes, respectively. The treatment time in Step 2 in Example 6 was 3 minutes.
  • the test for evaluation of the coating was conducted as specified in the aforesaid test procedure, with the following exceptions in each case: prior to crimping on the blind ferrule, the containers were filled with propellant 134a; crimp settings were 5.5 mm height and 17.6 mm diameter; after crimping containers were placed in a warm bath for 3 minutes at 55°C (normal manufacturing procedure to test for leaks) and cooled in the dry- ice for 15 minutes (cooling to allow for cutting the blind ferrule off containers with propellant inside).
  • Control containers are not subjected to the particle removal process step. All containers are then submitted for salbutamol sulphate assay by UV Spectrophotometry. Results are reported as percent of control deposition (amount of deposition on test container divided by amount of deposition on control container x 100%).
  • the containers were plasma treated similar to that described supra, however using a system provided with 16 nozzles for simultaneous treatment of 16 containers and the treatment including three steps using with the following conditions: Step 1 Oxygen Pretreatment:
  • Oxygen flow density 0.16 sccm/square cm (O 2 flow 100 seem)
  • Tetramethylsilane flow density 0.16 seem/ square cm (TMS flow 100 seem)
  • Plasma duration 4 minutes After completion of step 2, the flow of tetramethylsilane was stopped, and a flow of oxygen was introduced to initiate a post treatment with oxygen:
  • Step 3 Post Deposition Treatment:
  • Oxygen flow density 0.16 seem/ square cm (O 2 flow 100 seem)
  • Plasma duration 30 seconds
  • the reaction was monitored by gas chromatography (GC) to observe excess 3-aminopropyl- trimethoxysilane and Fourier transform infrared spectroscopy (FTIR) to observe unreacted ester functional groups and was found to be complete within 90 minutes after the addition of the 3-aminopropyltrimethoxysilane.
  • GC gas chromatography
  • FTIR Fourier transform infrared spectroscopy
  • the reaction product was stirred rapidly, and the pressure in the flask was reduced to 1 mmHg (133 Pa) gradually to minimize bumping.
  • Methanol by-product was distilled from the flask over a period of two hours, and BI was recovered from the flask.
  • the second listed silane (i.e., MONO) was be prepared using methods described in U.S. Patent No. 3,250,808 (Moore) and U.S. Patent No. 3,646,085 (Bartlett) (the contents of both documents incorporated in their entirety herein by reference).
  • the acid fluoride, C 3 F 7 O(CF(CF 3 )CF 2 O) 5 6 CF(CF 3 )-COF was prepared by the polymerization of hexafluoroproplyene oxide as described in U.S.
  • Example XX the acid fluoride was converted to the corresponding methyl ester via esterif ⁇ cation, i.e., by reacting the acid fluoride with excess methanol at around 20 0 C. Subsequently the methyl ester was reacted with 3-aminopropyltrimethoxysilane as described in U.S. 3,646,085 similar to Example 2.
  • C 3 F 7 O(CF(CF 3 )CF 2 O) 5 6 CF(CF 3 )C(O)OCH 3 (30Og) was added to an oven-dried 1000 ml round bottom flask under a nitrogen atmosphere and stirred rapidly at 65° using a magnetic stirrer.
  • 3-aminopropyltrimethoxysilane (44.41 g) was added to the flask in one portion.
  • the reaction was monitored by Fourier transform infrared spectroscopy (FTIR) to observe unreacted ester functional groups as well as the formation of desired product MONO.
  • FTIR Fourier transform infrared spectroscopy
  • the reaction was found to be complete after 16 hours.
  • Methanol by-product was removed by heating in a Rotavac at 75°C. Thereafter MONO was recovered from the flask. An aliquot of composition was placed in the plasma-coated container.
  • For compositions including a catalyst 2 drops of 10% dibutyl tin laurate catalyst in HFE/toluene were added to the aliquot.
  • the container was releasably closed and then shaken manually for approximately 1 minute. Thereafter excess composition in the container was removed. After this, the container was air-dried for 5 minutes, and then cured in an oven for 15 minutes at 200 C.
  • Oxygen flow density 0.32 sccm/square cm
  • Plasma duration 20 seconds
  • step 2 After completion of step 2, the flow of tetramethylsilane was stopped, and to initiate a post-fluorination-treatment on the outer- surface of the diamond-like glass coating deposited in step 2, a flow of sulfur hexafluoride was introduced:
  • Step 3 Post Deposition Treatment: sulfur hexafluoride flow density: 0.32 seem/ square cm
  • Plasma duration 30 seconds
  • the pressure within the container was maintained at around 740 mTorr (99 Pa), and then prior to and during step 3 the pressure was lowered to about 320 mTorr (42 Pa).
  • Aerosol formulation consisting of a dispersion of salbutamol sulfate particles (about 2 mg/ml) in HFA- 134a was cold- filled into containers to-be-tested and 50 mcl valves commercially available under the trade designation SPRA YMISER (3M Company) were crimped onto the containers. All canisters were placed in a 55°C water bath for 3 minutes, actuated 3 times to test valve function, and held at ambient conditions for approximately one week. The canisters were then fired down to completion (approximately 200-300 total shots), and thereafter the canisters were assayed for deposited salbutamol sulfate content.

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Abstract

L'invention porte sur un dispositif d'inhalation médical ou sur un composant de celui-ci qui possède un revêtement en verre de type diamant comportant de l'hydrogène et, sur une base sans hydrogène, environ 20 à environ 40 % en pourcentage atomique de silicium, plus de 39 % en pourcentage atomique de carbone, et moins de 33 % en pourcentage atomique d'oxygène pouvant aller jusqu'à zéro.
EP20100719859 2009-05-06 2010-05-06 Dispositif d'inhalation médical Withdrawn EP2427591A1 (fr)

Applications Claiming Priority (2)

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US17588709P 2009-05-06 2009-05-06
PCT/US2010/033847 WO2010129753A1 (fr) 2009-05-06 2010-05-06 Dispositif d'inhalation médical

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EP2427591A1 true EP2427591A1 (fr) 2012-03-14

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US (1) US8815325B2 (fr)
EP (1) EP2427591A1 (fr)
CN (1) CN102803555A (fr)
BR (1) BRPI1007675A2 (fr)
CA (1) CA2760801A1 (fr)
WO (1) WO2010129753A1 (fr)

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009061895A2 (fr) * 2007-11-06 2009-05-14 3M Innovative Properties Company Dispositifs d'inhalation médicaux et composants de ceux-ci
GB0721737D0 (en) * 2007-11-06 2007-12-19 3M Innovative Properties Co Medicinal inhalation devices and components thereof
WO2009079078A1 (fr) 2007-12-14 2009-06-25 Labogroup S.A.S. Administration de produits alimentaires sous forme d'aérosols
EP2427902B1 (fr) 2009-05-06 2017-01-18 3M Innovative Properties Company Appareil et procédé pour le traitement au plasma de contenants
US8664323B2 (en) 2010-06-25 2014-03-04 3M Innovative Properties Company Fluorinated composition, method of coating the composition, and article thereby
US20120234320A1 (en) * 2011-03-17 2012-09-20 O'ferrell Zachary W Metered Dose Inhaler Port for Ventilated Patients
US20130082074A1 (en) * 2011-10-03 2013-04-04 Graham Packaging Company, L.P. Plastic aerosol container assembly and method of making
KR101369381B1 (ko) * 2011-11-04 2014-03-06 에스케이이노베이션 주식회사 함불소 화합물을 포함하는 저굴절 코팅 조성물, 이를 이용한 반사방지 필름, 이를 포함하는 편광판 및 표시장치
US20130183435A1 (en) * 2012-01-13 2013-07-18 Hongmin Sun Low temperature plasma coating for anti-biofilm formation
GB201221063D0 (en) 2012-11-23 2013-01-09 3M Innovative Properties Co Metered dose dispensing valve
FR3003857B1 (fr) * 2013-03-28 2015-04-03 Quertech Procede de traitement par un faisceau d'ions pour produire des materiaux en verre superhydrophiles.
DE102013104549B4 (de) * 2013-05-03 2015-08-13 Chv Pharma Gmbh & Co. Kg Inhalator für ein Dosieraerosol
JP6451279B2 (ja) * 2014-03-31 2019-01-16 信越化学工業株式会社 フルオロポリエーテル基含有ポリマー変性シラン、表面処理剤及び物品
GB2536285A (en) * 2015-03-13 2016-09-14 3M Innovative Properties Co Coating process
CN106457305B (zh) * 2014-05-22 2020-06-02 3M创新有限公司 涂覆工艺
DE102014215064A1 (de) * 2014-07-31 2016-02-04 Pari GmbH Spezialisten für effektive Inhalation Vernebler
CN104225739A (zh) * 2014-09-30 2014-12-24 四川普锐特医药科技有限责任公司 一种医用定量吸入气雾剂
JP2018510099A (ja) 2015-04-01 2018-04-12 グレイアム パッケイジング カンパニー リミテッド パートナーシップ プラスチック圧力容器のネックフィニッシュ上にクロージャ組立体を封止する構造および方法
JP6390521B2 (ja) * 2015-06-03 2018-09-19 信越化学工業株式会社 フルオロポリエーテル基含有ポリマー変性シラン
US20190054010A1 (en) 2015-10-29 2019-02-21 3M Innovative Properties Company Formulation and aerosol canisters, inhalers, and the like containing the formulation
KR102648009B1 (ko) * 2015-12-14 2024-03-18 신에쓰 가가꾸 고교 가부시끼가이샤 플루오로폴리에터기 함유 폴리머 변성 실레인, 표면처리제 및 물품
US11207477B2 (en) 2017-05-17 2021-12-28 Kindeva Drug Delivery L.P. Formulation and aerosol canisters, inhalers, and the like containing the formulation
US11779716B2 (en) 2017-08-03 2023-10-10 Kindeva Drug Delivery L.P. Method for making medicinal delivery device having multi-layer coating
GB201717996D0 (en) * 2017-10-31 2017-12-13 Portal Medical Ltd Medicament dispenser device
US20210161804A1 (en) 2018-06-07 2021-06-03 Kindeva Drug Delivery L.P. Fluticasone and vilanterol formulation and inhaler
JP2021527057A (ja) 2018-06-07 2021-10-11 キンデーバ ドラッグ デリバリー リミティド パートナーシップ フルチカゾン及びビランテロール製剤並びに吸入器
US12220525B2 (en) 2018-06-27 2025-02-11 Kindeva Drug Deliver L.P. Tiotropium formulation and inhaler
EP3880169B1 (fr) 2018-11-12 2025-07-23 Kindeva Drug Delivery L.P. Formulation d'umeclidinium et vilanterol et inhalateur
EP3756711A1 (fr) * 2019-06-25 2020-12-30 Presspart Gmbh & Co. Kg Procédé de nettoyage au plasma et de revêtement des boîtes mdi
KR102473239B1 (ko) * 2019-09-02 2022-12-01 (주)인트인 공기질 정보를 이용하여 호흡기 치료 정보를 제공하는 건강 관리 시스템 및 건강 관리 서버
EP4063334A1 (fr) * 2021-03-25 2022-09-28 Schott Ag Élément en verre revêtu
US12269645B2 (en) * 2021-03-25 2025-04-08 Schott Ag Coated glass element
JP2024536993A (ja) 2021-09-08 2024-10-10 キンデーバ ドラッグ デリバリー リミティド パートナーシップ 定量吸入器及び懸濁組成物
WO2024181972A1 (fr) 2022-03-01 2024-09-06 Kindeva Drug Delivery L.P. Inhalateurs à dose et suspensions à haute dose
AU2024230822A1 (en) 2023-03-02 2025-10-16 Breath Of Life International Ltd Metered dose inhalers and solutions including cannabinoids in hfo-1234ze(e)
AU2024230006A1 (en) 2023-03-02 2025-09-18 Kindeva Drug Delivery L.P. Metered dose inhalers and solutions including cannabinoids in hfa-152a

Family Cites Families (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA725747A (en) 1966-01-11 N. Short James Preparation of random copolymers
US3250808A (en) 1963-10-31 1966-05-10 Du Pont Fluorocarbon ethers derived from hexafluoropropylene epoxide
US3810874A (en) 1969-03-10 1974-05-14 Minnesota Mining & Mfg Polymers prepared from poly(perfluoro-alkylene oxide) compounds
US3646085A (en) 1970-09-24 1972-02-29 Du Pont Perfluoroalkyletheramidoalkyltrialkoxysilanes
DE3832692A1 (de) 1988-09-27 1990-03-29 Leybold Ag Dichtungselement mit einem absperrkoerper aus einem metallischen oder nichtmetallischen werkstoff und verfahren zum auftragen von hartstoffschichten auf den absperrkoerper
US4980196A (en) 1990-02-14 1990-12-25 E. I. Du Pont De Nemours And Company Method of coating steel substrate using low temperature plasma processes and priming
DE69231787T2 (de) 1991-01-28 2001-08-02 Matsushita Electric Industrial Co., Ltd. Medizinischer Artikel und Verfahren zu seiner Herstellung
US6596260B1 (en) 1993-08-27 2003-07-22 Novartis Corporation Aerosol container and a method for storage and administration of a predetermined amount of a pharmaceutically active aerosol
EP1908488A3 (fr) 1995-04-14 2008-04-16 SmithKline Beecham Corporation Inhalateur de dose mesurée pour le salmétérol
DE69631476T2 (de) 1995-04-14 2005-01-13 Smithkline Beecham Corp. Vorrichtung zur dosierten inhalierung von beclomethason-diproprionat
WO1996032151A1 (fr) 1995-04-14 1996-10-17 Glaxo Wellcome Inc. Inhalateur doseur de propionate fluticasone
BR9604976A (pt) 1995-04-14 1998-06-09 Glaxo Wellcome Inc Inalador de dose medida sistema inalador de dose medida e uso do mesmo
DE69705583T2 (de) 1996-05-06 2002-06-06 Eli Lilly And Co., Indianapolis Antivirusverbindungen
US6632805B1 (en) 1996-05-07 2003-10-14 Emory University Methods for using water-stabilized organosilanes
US6156689A (en) 1997-10-23 2000-12-05 Phillips Petroleum Company Catalyst composition comprising zinc compound or boron compound and hydrocarbon conversion process
AU2001256168A1 (en) 2000-03-01 2001-09-12 Glaxo Group Limited Metered dose inhaler
EP1259276A2 (fr) 2000-03-01 2002-11-27 Glaxo Group Limited Aerosol-doseur
AU4417101A (en) 2000-03-01 2001-09-12 Glaxo Group Limited Metered dose inhaler
AU4831801A (en) 2000-03-01 2001-09-12 Glaxo Group Limited Metered dose inhaler
US6696157B1 (en) * 2000-03-05 2004-02-24 3M Innovative Properties Company Diamond-like glass thin films
GB0025092D0 (en) 2000-10-13 2000-11-29 Glaxo Group Ltd Medicament dispenser
SE0004610D0 (sv) 2000-12-13 2000-12-13 Astrazeneca Ab Surface modification process
WO2003006181A1 (fr) 2001-07-10 2003-01-23 3M Innovative Properties Company Dispositifs d'inhalation de medicaments et composants a revetement forme par depot chimique en phase vapeur thermique
GB0122725D0 (en) 2001-09-21 2001-11-14 Glaxo Group Ltd Drug dispensing components
US7196212B2 (en) 2001-10-05 2007-03-27 Shin-Etsu Chemical Co., Ltd. Perfluoropolyether-modified silane, surface treating agent, and antireflection filter
US6592659B1 (en) 2001-11-15 2003-07-15 3M Innovative Properties Company Compositions for aqueous delivery of fluorinated silanes
US6878419B2 (en) 2001-12-14 2005-04-12 3M Innovative Properties Co. Plasma treatment of porous materials
FI20020909A0 (fi) * 2002-05-14 2002-05-14 Perlos Oyj Inhalaattori, inhalaattorin komponentti ja menetelmä sellaisen valmistamiseksi
US20050133025A1 (en) * 2002-05-14 2005-06-23 Juha Laiho Inhalator and method of manufacturing same
US7553514B2 (en) 2006-08-28 2009-06-30 3M Innovative Properties Company Antireflective article
US7891636B2 (en) 2007-08-27 2011-02-22 3M Innovative Properties Company Silicone mold and use thereof
GB0721737D0 (en) 2007-11-06 2007-12-19 3M Innovative Properties Co Medicinal inhalation devices and components thereof
WO2009061895A2 (fr) 2007-11-06 2009-05-14 3M Innovative Properties Company Dispositifs d'inhalation médicaux et composants de ceux-ci
GB0721739D0 (en) 2007-11-06 2007-12-19 3M Innovative Properties Co medicinal inhalation devices and components thereof
US20120097159A1 (en) 2009-05-06 2012-04-26 Suresh Iyer Medicinal inhalation devices and components thereof
EP2427902B1 (fr) 2009-05-06 2017-01-18 3M Innovative Properties Company Appareil et procédé pour le traitement au plasma de contenants

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2010129753A1 *

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WO2010129753A1 (fr) 2010-11-11
US8815325B2 (en) 2014-08-26
US20120103330A1 (en) 2012-05-03

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